curcumin and Carcinoma

Despite the use of surgical resection and aggressive chemotherapy, nearly 50% of patients with colorectal carcinoma develop recurrent disease, highlighting the need for improved therapies. Curcumin (diferuloylmethane), the major active ingredient of turmeric (curcuma longa) with no discernable toxicity, has been shown to inhibit the growth of transformed cells and colon carcinogenesis at the initiation, promotion, and progression stages in carcinogen-induced rodent models. In a Phase I clinical trial, curcumin has been found to be extremely well tolerated and effective. In this review, we summarized the current status of our knowledge about the effectiveness of curcumin when given in combination with current chemotherapeutics such as 5-fluorouracil, oxaliplatin, and gemcitabine in treatment of gastrointestinal cancers with particular reference to colorectal cancer. Existing data suggest that curcumin in combination with chemotherapy is a superior strategy for treatment of gastrointestinal cancer.

Topics: Adenoma; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Colorectal Neoplasms; Curcumin; Deoxycytidine; Fluorouracil; Gastrointestinal Neoplasms; Gemcitabine; Humans; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome

Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available. This is of vital importance to implement chemoprevention strategies. This study aimed to quantify levels of curcuminoids in colorectal mucosa of patients undergoing colorectal endoscopy or surgical resection and to obtain information on the acceptability and compliance with daily curcumin. Curcumin C3 complex (2.35 g) was administered to patients once daily for 14 days before endoscopic biopsy or colonic resection. Safety and tolerance were monitored. Analysis of curcuminoids in plasma, urine, and colonic mucosa was conducted by ultraperformance liquid chromatography (UPLC)-UV with characterization by liquid chromatography/tandem mass spectrometry (LC/MS-MS). Twenty-four of 26 patients commencing curcumin completed the course. Six patients reported mild gastrointestinal adverse events. Curcuminoids were detectable in nine of 24 plasma samples, 24 of 24 urine samples, and in the colonic mucosa of all 23 biopsied participants. Mean tissue levels were 48.4 μg/g (127.8 nmol/g) of parent curcuminoids. The major conjugate, curcumin glucuronide, was detectable in 29 of 35 biopsies. High levels of topical curcumin persisted in the mucosa for up to 40 hours postadministration. Sixteen participants (67%) stated that they would take curcumin long-term should it be of proven benefit. In summary, pharmacologically active levels of curcumin were recovered from colonic mucosa. The regimen used here seems safe, and patients support its use in long-term trials.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Biological Availability; Carcinoma; Colon; Colorectal Neoplasms; Curcumin; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Patient Acceptance of Health Care; Patient Compliance; Pilot Projects; Time Factors

Since the improvement of chemotherapy with safe molecules is needed for a better efficacy without supplementary toxicity, we investigated the feasibility and tolerability of the combination of docetaxel and curcumin, a polyphenolic derivative extracted from Curcuma longa root.. Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, three dose-limiting toxicities were observed and two out of three patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8,000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with five PR and three SD. Some improvements as biological and clinical responses were observed in most patients.. Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m(2)) was administered as a 1 h i.v. infusion every 3 w on d 1 for six cycles. Curcumin was orally given from 500 mg/d for seven consecutive d by cycle (from d-4 to d+2) and escalated until a dose-limiting toxicity should occur. The primary endpoint of this study was to determine the maximal tolerated dose of the combination of dose-escalating curcumin and standard dose of docetaxel chemotherapy in advanced and metastatic breast cancer patients. Secondary objectives included toxicity, safety, vascular endothelial growth factor and tumor markers measurements and assessment of objective and clinical responses to the combination therapy.. The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 w in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Breast Neoplasms, Male; Carcinoma; Curcumin; Diarrhea; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Follow-Up Studies; Humans; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neutropenia; Taxoids; Time Factors; Treatment Outcome

The goal of this study was to evaluate if combinations of ingredients with known anti-cachexia benefits (Fish oil-FO with either curcumin or Green tea extract-GTE), have adverse effects on tumor growth, using human carcinoma xenograft mice models. FO (EPA/DHA 360 mg/kg bw), GTE (90 mg/kg bw), and curcumin (180 mg/kg bw) were administered orally, alone or in combination, to nude mice bearing either A549 human non-small cell lung carcinoma or SW620 human colon carcinoma tumors. Bodyweight, tumor growth, survival time, and other clinical endpoints were assessed. The ingredients either alone or in combinations were well tolerated in both lung and colon tumor-bearing mice. There were no significant group differences between individual or combination treatments for tumor growth (A549 or SW620) as measured by the median time in days to endpoint of tumor volume (TTE). TTE results indicate that these ingredients (alone or combinations) did not adversely impact tumor growth. No significant differences in body weights or survival were observed between controls and treatment groups indicating no adverse health effects of the ingredients. In conclusion, FO, GTE or curcumin administered as monotherapies and in combination were well tolerated and displayed no adverse effects on tumor growth in mouse xenograft models of lung and colon cancer.

Topics: Animals; Carcinoma; Colonic Neoplasms; Curcumin; Fish Oils; Heterografts; Humans; Lung; Mice; Mice, Nude; Plant Oils; Polyphenols

The efficacy of photodynamic therapy (PDT) is still limited by the inefficient utilisation of generated ROS in tumours due to cellular redox homeostasis. To improve the therapeutic efficacy for oral carcinoma, biomimetic cell membrane-coated mesoporous nanoplatform was tailored to interfere with cellular redox homeostasis for amplified PDT. In this study, CAL-27 cancer cell membrane (CM) was encapsulated onto the mesoporous silica NPs (MSN), which were preloaded with Chlorin e6 (Ce6) and Curcumin (Cur). The biomimetic nanoparticles displayed a size of around 120 nm, which had excellent cytotoxicity under a laser and increased uptake ability to tumour cell. After internalised by cancer cells, the released Cur could effectively disturb ROS-defence system by suppressing TrxR activity, and decreasing TrxR-2 expression (

Topics: Carcinoma; Cell Line, Tumor; Cell Membrane; Curcumin; Homeostasis; Humans; Mouth Neoplasms; Nanoparticles; Oxidation-Reduction; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species

The therapeutic activity of paclitaxel against ovarian carcinoma is relatively low due to the frequent occurrence of chemoresistance and disease recurrence. We found earlier that a combination of curcumin and paclitaxel reduces cell viability and promotes apoptosis in paclitaxel-resistant (i.e., taxol-resistant, Txr) ovarian cancer cells. In the present study, we first used RNA sequencing (RNAseq) analysis to identify genes that are upregulated in Txr cell lines but downregulated by curcumin in ovarian cancer cells. The nuclear factor kappa B (NFκB) signaling pathway was shown to be upregulated in Txr cells. Furthermore, based on the protein interaction database BioGRID, we found that Smad nuclear interacting protein 1 (SNIP1) may be involved in regulating the activity of NFκB in Txr cells. Accordingly, curcumin upregulated SNIP1 expression, which in turn downregulated the pro-survival genes Bcl-2 and Mcl-1. Using shRNA-guided gene silencing, we found that SNIP1 depletion reversed the inhibitory effect of curcumin on NFκB activity. Moreover, we identified that SNIP1 enhanced NFκB protein degradation, thereby suppressing NFκB/p65 acetylation, which is involved in the inhibitory effect of curcumin on NFκB signaling. The transcription factor early growth response protein 1 (EGR1) was shown to represent an upstream transactivator of SNIP1. Consequently, we show that curcumin inhibits NFκB activity by modulating the EGR1/SNIP1 axis to attenuate p65 acetylation and protein stability in Txr cells. These findings provide a new mechanism to account for the effects of curcumin in inducing apoptosis and reducing paclitaxel resistance in ovarian cancer cells.

Topics: Carcinoma; Cell Line, Tumor; Curcumin; Drug Resistance, Neoplasm; Female; Humans; Neoplasm Recurrence, Local; NF-kappa B; Ovarian Neoplasms; Paclitaxel; RNA-Binding Proteins

In this study, we observed that in human colon carcinoma HCT116 cells mRNA level of the human β-galactoside α2,6-sialyltransferase (hST6Gal I) was decreased by curcumin. FACS analysis using the α2,6-sialyl-specific lectin (SNA) also showed a noticeable decrease in binding to SNA by curcumin.. To investigate the mechanism for curcumin-triggered downregulation of hST6Gal I transcription.. The mRNA levels of nine kinds of hST genes were assessed by RT-PCR after curcumin was treated in HCT116 cells. The level of hST6Gal I product on cell surface was examined by flow cytometry analysis. Luciferase reporter plasmids with 5'-deleted constructs and mutants of the hST6Gal I promoter were transiently transfected into HCT116 cells, and the luciferase activity was measured after treatment with curcumin.. Curcumin led to significant transcriptional repression of the hST6Gal I promoter. Promoter analysis using deletion mutants proved that the - 303 to - 189 region of the hST6Gal I promoter is required for transcriptional repression in response to curcumin. Among putative binding sites for transcription factors IK2, GATA1, TCF12, TAL1/E2A, SPT, and SL1 in this region, by site-directed mutagenesis analysis the TAL/E2A binding site (nucleotides - 266/- 246) was proved to be crucial for curcumin-triggered downregulation of hST6Gal I transcription in HCT116 cells. The transcription activity of hST6Gal I gene in HCT116 cells was markedly suppressed by compound C, an AMP-activated protein kinase (AMPK) inhibitor.. These indicate that gene expression of hST6Gal I in HCT116 cells is controlled through AMPK/TAL/E2A signal pathway.

Topics: AMP-Activated Protein Kinases; beta-D-Galactoside alpha 2-6-Sialyltransferase; Carcinoma; Colonic Neoplasms; Curcumin; HCT116 Cells; Humans; Luciferases; RNA, Messenger

Curcumin is a bioactive component with anticancer characteristics; nevertheless, it has poor solubility and fast metabolism, resulting in low bioavailability and so restricting its application. Curcumin loaded in nano emulsions (Cur-NE) was developed to improve water solubility and eliminate all the limitations of curcumin. Size distribution, zeta potential, transmission electron microscopy (TEM) measurements, UV-Visible spectra, IR spectra and thermogravimetric analysis (TGA), were used to characterize the prepared Cur-NE. Cancer therapeutic efficacy was assessed by oxidative stress (superoxide dismutase (SOD), Glutathione-S-Transferase (GST), malondialdehyde (MDA) and nitric oxide (NO), DNA damage, apoptotic proteins (caspase-3 and 9), besides investigating tumor histology and monitoring tumor growth. Additionally, the cytotoxicity and genotoxicity of the liver, kidney, heart, and spleen tissues were examined to gauge the adverse effects of the treatment method's toxicity. The results showed that Cur-NE is more effective than free curcumin at slowing the growth of Ehrlich tumors while significantly increasing the levels of apoptotic proteins. On the other hand, Cur-NE-treated mice showed some damage in other organs when compared to mice treated with free curcumin. Cur-NE has a higher efficacy in treating Ehrlich tumor.

Topics: Animals; Ascites; Carcinoma; Curcumin; Emulsions; Liver; Mice; Nanoparticles; Particle Size

We investigated the apoptotic effects of curcumin in the colon carcinoma cell line SW480.. Cells were treated with 40-200 μM curcumin for 24, 48, and 72 h, and the IC. These results suggest that curcumin may be a potential protective or treatment agent against colon cancer; however, further studies on curcumin-rich diets and curcumin bioavailability are required.

Topics: Apoptosis; Carcinoma; Caspase 3; Caspase 8; Caspases; Cell Line, Tumor; Cell Proliferation; Colon; Colonic Neoplasms; Curcumin; Humans

Cell viability, glycolytic activity, Annexin V-PE binding activity, reactive oxygen species levels, mitochondrial membrane potential, ATP content, Western blot analysis, and spheroid viability were measured for this study.. Acidic pH-tolerant prostate cancer cells, PC-3AcT and DU145AcT, increased cytotoxicity with ERK1/2 inhibition in a curcumin concentration-dependent manner at concentrations that resulted in >90% cell viability in normal prostate epithelial HPrEC cells. ERK1/2 inhibition by curcumin and/or PD98059 suppressed cell growth, reduced glucose consumption, and downregulated the expression of key regulatory enzymes in glucose metabolism including hexokinases, phosphofructokinase, and pyruvate dehydrogenase. In addition, these compounds caused loss of mitochondrial membrane potential with increased intracellular ROS levels, decreased levels of complexes I, III, and IV in the mitochondrial electron transport chain, and cellular ATP depletion, leading to upregulation of marker proteins in apoptosis (cleaved caspase-3 and cleaved PARP) and necroptosis (p-MLKL and p-RIP3). The results of curcumin and/or PD98059 treatment in 3D cultures showed similar trends to those in 2D cultures.. Taken together, the results provide mechanistic evidence for the antiglycolytic and cytotoxic roles of curcumin through inhibition of the MEK/ERK signaling pathway in prostate carcinoma cells preadapted to acidic conditions.

Topics: Adenosine Triphosphate; Carcinoma; Cell Line, Tumor; Curcumin; Glycolysis; Humans; Male; MAP Kinase Signaling System; Prostate; Prostatic Neoplasms

The synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average -9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and

Topics: Adenocarcinoma of Lung; Alkadienes; Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Screening Assays, Antitumor; ErbB Receptors; Female; Heat-Shock Proteins; Humans; Ligands; Lung Neoplasms; Molecular Docking Simulation; Molecular Structure; Ovarian Neoplasms; Reactive Oxygen Species; Spectroscopy, Fourier Transform Infrared; Structure-Activity Relationship; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Three new derivatives of tetrahydrocurcumin

Topics: Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Copper; Curcumin; Drug Screening Assays, Antitumor; Etoposide; Humans; Molecular Structure; Structure-Activity Relationship

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.

Topics: Animals; Antibiotics, Antineoplastic; Capsules; Carcinoma; Colonic Neoplasms; Curcumin; Doxorubicin; Liposomes; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Particle Size; Rats

This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing.

Topics: Antineoplastic Agents, Phytogenic; Biological Dressings; Breast Neoplasms; Carcinoma; Cell Cycle; Cellulose; Curcumin; Cyclin D1; Drug Carriers; Drug Liberation; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; Hydrogels; MCF-7 Cells; Melanocytes; Membranes, Artificial; Models, Molecular; Molecular Docking Simulation; Nanoparticles; Polyvinyl Alcohol; Protein Conformation; Spectroscopy, Fourier Transform Infrared; Wound Healing; X-Ray Diffraction

This study is to explore the role of curcumin and GLUT-1 antisense oligodeoxynucleotides (AS-ODN) on autophagy modulation-initiated radiosensitivity.. BALB/c mice were employed to establish xenograft model using Tu212 cell. The expression of autophagy- and apoptosis-related proteins was determined by WB. Autophagosome was observed under transmission electron microscope. Apoptosis of tumor tissue were detected by TUNEL staining.. Combinations of curcumin and GLUT-1 AS-ODN with 10 Gy inhibited the tumor growth by inducing apoptosis of laryngeal cancer cells followed with the enhancement of autophagy. 3-MA also had a promotion effect on irradiation-mediated growth inhibition possibly by depressing PI3K and on curcumin/GLUT-1 AS-ODN-mediated growth inhibition potentially by regulating autophagic events. Of note, a de-escalation of radiotherapy dose (5 Gy) along with curcumin, GLUT-1 AS-ODN or 3-MA produced a stronger effect than high dosage of radiotherapy (10 Gy) alone.. Curcumin and GLUT-1 AS-ODN improve the radiosensitivity of laryngeal carcinoma through regulating autophagy and inducing apoptosis.

Topics: Animals; Apoptosis; Autophagy; Carcinoma; Cell Line, Tumor; Curcumin; Glucose Transporter Type 1; Laryngeal Neoplasms; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides; Radiation Tolerance; Radiation-Sensitizing Agents

Topics: Carcinoma; Curcumin; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms

Laryngeal carcinoma remains one of the most common malignancies, and curcumin has been proven to be effective against head and neck cancers in vitro. However, it has not yet been applied in clinical settings due to its low stability. In the current study, we synthesized 34 monocarbonyl analogues of curcumin with stable structures. CA15, which exhibited a stronger inhibited effect on laryngeal cancer cells HEp-2 but a lower toxicity on hepatic cells HL-7702 in MTT assay, was selected for further analysis. The effects of CA15 on cell viability, proliferation, migration, apoptosis, and NF-

Topics: Apoptosis; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Curcumin; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; Laryngeal Neoplasms; NF-kappa B; Quinoxalines; Tumor Necrosis Factor-alpha

Curcumin, a derivative from the dried rhizome of curcuma longa, has been proven to possess anti-tumor effects. However, the detailed molecular mechanisms have not been fully elucidated. In this study, we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer. BALB/C mice grafted with a mouse gastric adenocarcinoma cell line (MFC) were used as the experimental model. Mice received different doses of curcumin after grafting. Tumor size was measured and tumor weight was determined after tumor inoculation. TUNEL assay and flow cytometric analysis were applied to evaluate the apoptosis of the cancer cells. Serum cytokines IFN-γ, TNF-α, granzyme B and perforin were detected by ELISA assay. The anti-tumor effect was determined using cytotoxic T-lymphocyte (CTL) assays and in vivo tumor prevention tests. The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system. Compared with controls, tumor growth (size and weight) was significantly inhibited by curcumin treatment (P < 0.05). The apoptotic index in gastric cancer cells was significantly increased in the curcumin treatment group. Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline (P < 0.01). The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was down-regulated after curcumin treatment. Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells, activating immune cells to secrete a large amount of cytokines, and down-regulating the DEC1, HIF-1α, VEGF and STAT3 signal transduction pathways.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Mice; Mice, Inbred BALB C; Plant Extracts; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms; Tumor Necrosis Factor-alpha

Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment.

Topics: Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Curcumin; Down-Regulation; Epithelial-Mesenchymal Transition; Humans; Signal Transduction; Thyroid Cancer, Papillary; Thyroid Neoplasms; Transforming Growth Factor beta; Transforming Growth Factor beta3

Curcumin shows growth-inhibition against tumor cells through multi-target mechanisms. Nevertheless, the poor stability and pharmacokinetics considerably limit its clinical functions. Increased effort has been put into the chemical alteration of curcumin to find potential analogues with improved bioavailability and antitumor activities. In this study, the antitumor activity of a novel curcuminoid (B63) in nasopharyngeal carcinoma (NPC) was examined. The MTT and colony formation assays were used to detect NPC cell viability and proliferation. Flow cytometry was used to detect cell cycle distribution. The Annexin V/PI staining assay and cleavage PARP and cleavage caspase-3 expression were used to examine apoptosis. Western blotting was used to examine the protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP. The suppressive effect of B63 on tumor growth was examined in vivo by subcutaneously inoculated NPC in a tumor model using nude mice. Treatment with B63 potentially caused growth inhibition and apoptosis in NPC cells in a dose- and time-responsive manner. Its antitumor effect was associated with the ER stress activation. Nevertheless, the same dose of curcumin did not activate ER stress. In addition, knockdown of Chop attenuated B63-induced cell viability inhibition, suggesting that the apoptotic pathway is ER stress-dependent. The tumor volume and weight were significantly reduced by pretreating the NPC cells with B63 before implantation in the in vivo mouse model. B63 exhibited a more potent antitumor action than curcumin in NPC. These observations on the novel compound B63 indicate a novel candidate for NPC therapy.

Topics: Activating Transcription Factor 4; Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Humans; Mice; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Time Factors; Transcription Factor CHOP; X-Box Binding Protein 1; Xenograft Model Antitumor Assays

Curcumin, traditionally used as food and medicinal purposes, has recently been reported to have protective efficacy against hypoxia. Hypoxia is one of the important reactive factors in tumor metastasis, which is a key problem in clinical thyroid cancer therapy. In present study, we investigate the anti-metastatic effect of curcumin on the K1 papillary thyroid cancer cells as well as its potential mechanisms. The results show that curcumin effectively inhibits hypoxia-induced reactive oxygen species (ROS) upregulation and significantly decreases the mRNA and protein expression levels of hypoxia-inducible factor-1α (HIF-1α) in K1 cells. Curcumin also decreases the DNA binding ability of HIF-1α to hypoxia response element (HRE). Furthermore, curcumin enhances E-cadherin expression, inhibits metalloproteinase-9 (MMP-9) enzyme activity, and weakens K1 cells migration under hypoxic conditions. In summary, these results indicate that curcumin possesses a potent anti-metastatic effect and might be an effective tumoristatic agent for the treatment of aggressive papillary thyroid cancers.

Topics: Antineoplastic Agents; Blotting, Western; Carcinoma; Carcinoma, Papillary; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Curcumin; Electrophoretic Mobility Shift Assay; Humans; Neoplasm Invasiveness; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Thyroid Cancer, Papillary; Thyroid Neoplasms

Prostate cancer (PC) is a prevalent cancer in aged men. Curcumin is an active ingredient that has been extracted from the rhizome of the plant Curcuma longa. Recently, a potential of Curcumin against PC has been reported in PC, whereas the underlying molecular mechanisms are not completely understood. Here, we studied the effects of low-dose Curcumin on PC cell growth. Curcumin (from 0.2 to 0.8 μmol/l) dose-dependently inhibited the proliferation of PC cells, without affecting cell apoptosis. Further analyses showed that Curcumin dose-dependently increased a cell cycle suppressor CDKN1A at protein levels, but not mRNA levels, in PC cells, suggesting that Curcumin may regulate the translation of CDKN1A, as well as a possible involvement of miRNA intervention. From all CDKN1A-3'-UTR-binding miRNAs, we found that miR-208 was specifically inhibited in PC cells dose-dependently by Curcumin. Moreover, miR-208 was found to bind CDKN1A to suppress its expression. In a loss-of-function experiment, PC cells that overexpressed miR-208 failed to decrease cell proliferation in response to Curcumin. Together, these data suggest that Curcumin inhibits growth of PC via miR-208-mediated CDKN1A activation.

Topics: Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Prostatic Neoplasms; Protein Binding

Long non-coding RNAs (lncRNAs) are aberrantly expressed and have important functions in pathological processes. The present study investigated the lncRNA profiles and the effects of curcumin (Cur) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells. The lncRNA and mRNA profiles of each cell group were described by microarray analysis. Numerous differentially expressed genes were observed by microarrays in three cell groups. Cur significantly reversed the IR-induced lncRNA and mRNA expression signatures, shown by clustering analysis. Moreover, 116 of these IR-induced and Cur-reversed differentially expressed lncRNAs were obtained. Six lncRNAs (AF086415, AK095147, RP1-179N16.3, MUDENG, AK056098 and AK294004) were confirmed by qPCR. Furthermore, functional studies showed that lncRNA AK294004 exhibited a negative effect on cyclin D1 (CCND1), indicating that CCND1 might be a direct target of AK294004. IR-induced differentially expressed lncRNAs were reversed during Cur-enhanced radiosensitization in NPC cells, suggesting that lncRNAs have important functions in IR-induced radioresistance. Thus, Cur could serve as a good radiosensitizer.

Topics: Carcinoma; Cell Line, Tumor; Curcumin; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Radiation Tolerance; RNA, Long Noncoding; RNA, Messenger

Curcumin, one of the main bioactive components extracted from a traditional Chinese medicinal herb, exhibits potent anticancer activity against many types of cancer cells including nasopharyngeal carcinoma (NPC). However, the detailed molecular mechanism underlying this is not clearly understood. In this study, we showed that curcumin significantly inhibited the growth of NPC cells in a dose- and time-dependent manner as determined by MTT assays, while increasing apoptosis was also observed as measured by flow cytometry for the FITC-Annexin V and propidium iodide (PI) label and Hoechst 33258 staining. To further explore the potential mechanism, we showed that curcumin increased the phosphorylation of ERK1/2 but not p38 MAPK in a time-dependent manner, and induced protein expression of the tumor suppressors FOXO3a and p53 in a dose‑dependent manner, which were not observed in the presence of PD98059, an inhibitor of ERK1/2. Furthermore, silencing of FOXO3a and p53 genes by siRNAs overcame the inhibitory effect of curcumin on cell proliferation. Silencing or blockade of p53 using siRNA or chemical inhibitor abrogated the effect of curcumin on expression of FOXO3a protein; silencing or overexpression of FOXO3a had no further effect on curcumin-induced p53 protein expression. Furthermore, blockade of ERK1/2 and exogenous expression of FOXO3a restored the effect of curcumin on growth of cells. Together, our studies show that curcumin inhibits growth and induces apoptosis of NPC cells through ERK1/2-mediated increase in the protein expression and interaction of p53 and FOXO3a. p53 is upstream of FOXO3a, which form a regulatory loop that mediates the effect of curcumin. This study unveils a new mechanism by which curcumin inhibits the proliferation and induces apoptosis of human NPC cells.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Flavonoids; Forkhead Box Protein O3; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Humans; MAP Kinase Signaling System; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Phosphorylation; Tumor Suppressor Protein p53

Internalization of drugs by cancer cells is a crucial factor to impact cancer treatment effect. Curcumin, having inhibitory effect on a variety of cancers, was encapsulated into micelles of six-arm star-shape poly(ε-caprolactone)-b-poly(2-methacryloyloxyethylphosphorylcholine) (6sPCL-PMPC) in order to enhance its concentration in blood and cellular uptake. Micelles and curcumin-loaded micelles were prepared by the solvent-evaporation method. Drug-loading content and drug-loading efficiency could be achieved as high as 18.9 and 98%. MTT results showed that these curcumin-loaded micelles displayed significant cell cytotoxicity, while these blank micelles were noncytotoxic. The curcumin-loaded 6sPCL-PMPC micelles showed higher efficiency to kill HeLa cells than that of curcumin-loaded PCL-PEG micelles. The cellular uptake study indicated that the curcumin encapsulated into 6sPCL-PMPC micelles was ingested more by HeLa cells than the curcumin encapsulated into PCL-PEG micelles. In conclusion, the micelles with phosphatidylcholine (PC) groups as their exterior can greatly enhance the uptake by HeLa cells and the cytotoxicity of curcumin due to excellent internalization by cancer cells.

Topics: Antineoplastic Agents; Calorimetry, Differential Scanning; Carcinoma; Curcumin; Drug Carriers; Ethylene Oxide; Female; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Lactones; Micelles; Neoplasms, Glandular and Epithelial; Phosphatidylcholines; Spectrum Analysis

Curcumin, the major yellow-orange pigment of turmeric derived from the rhizome of Curcuma longa, is a highly pleiotropic molecule with the potential to modulate inflammation, oxidative stress, cell survival, cell secretion, homeostasis and proliferation. Curcumin, at relatively high concentrations, was repeatedly reported to be a potent inducer of apoptosis in cancer cells and thus considered a promising anticancer agent. In the present paper, the effects of low concentrations of curcumin on human cervical cancer (HeLa) cells were studied. We found curcumin-mediated decrease in the cell number and viability, and increase in apoptotic events and superoxide level. In contrast to previously shown curcumin cytotoxicity toward different cervical cancer lines, we observed toxic effects when even as low as 1 μM concentration of curcumin was used. Curcumin was not genotoxic to HeLa cells. Because argyrophilic nucleolar protein (AgNOR protein) expression is elevated in malignant cells compared to normal cells reflecting the rapidity of cancer cell proliferation, we evaluated curcumin-associated changes in size (area) and number of silver deposits. We showed curcumin-induced decrease in AgNOR protein pools, which may be mediated by global DNA hypermethylation observed after low concentration curcumin treatment. In summary, we have shown for the first time that curcumin at low micromolar range may be effective against HeLa cells, which may have implications for curcumin-based treatment of cervical cancer in humans.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma; Cell Proliferation; Cell Shape; Cell Survival; Cells, Cultured; Curcumin; Dose-Response Relationship, Drug; Female; HeLa Cells; Humans; Nucleolus Organizer Region; Uterine Cervical Neoplasms

The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur- NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrug- resistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo.. First, we determined the MDR- reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions.. The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions.. Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.

Topics: Animals; Antibodies; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biocompatible Materials; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Drug Delivery Systems; Drug Resistance, Neoplasm; Female; Humans; Lactic Acid; Mice; Mice, Inbred BALB C; Nanoparticles; Paclitaxel; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Uterine Cervical Neoplasms

Curcumin, the active constituent of dietary spice turmeric, possesses a strong potential for cancer prevention and treatment. However, there is no study to address the effects of curcumin on invasion and metastasis of thyroid cancers. Thyroid cancer is the most common malignancy of endocrine organs, and its incidence rates have steadily increased over recent decades. Although most indolent tumours can be effectively managed, metastatic tumours at distant secondary sites behave aggressively and currently there is no effective form of treatment. Here, for the first time it has been reported that curcumin inhibit multiple metastasis steps of K1 papillary thyroid cancer cells. Curcumin dose-dependently suppressed viability of K1 cells as well as its cell attachment, spreading, migration and invasion abilities. Moreover, curcumin could also down-regulate the expression and activity of matrix metalloproteinase-9 (MMP-9). The findings showed that curcumin might be an effective tumouristatic agent for the treatment of aggressive papillary thyroid carcinomas.

Topics: Carcinoma; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Curcumin; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neoplasm Metastasis; Thyroid Cancer, Papillary; Thyroid Neoplasms

Proprotein convertases (PCs) form a group of serine endoproteases that are essential for the activation of proproteins into their active form. Some PCs have been proposed to be potential therapeutic targets for cancer intervention because elevated PC activity has been observed in many different cancer types and because many of the PC substrates, such as pro-IGF-1R, pro-TGF-beta, pro-VEGF, are involved in signaling pathways related to tumor development. Curcumin, reported to possess anticancer activity, also affects many of these pathways. We therefore investigated the effect of curcumin on PC activity. Our results show that curcumin inhibits PC activity in a cell lysate-based assay but not in vitro. PC zymogen maturation in the endoplasmic reticulum appears to be inhibited by curcumin. Treating cells with thapsigargin or cyclopiazonic acid, two structurally unrelated inhibitors of the sarco- and endoplasmic reticulum Ca(2+)ATPase (SERCA), also hampered both the PC zymogen maturation and the PC activity. Importantly, curcumin, like the SERCA inhibitors, impaired ATP-driven (45)Ca(2+) uptake in the endoplasmic reticulum. These results indicate that curcumin likely restrains PC activity by inhibiting SERCA-mediated Ca(2+)-uptake activity. Experiments in three colon cancer cell lines confirm that curcumin inhibits both the (45)Ca(2+) uptake and PC activity, notably the processing of pro-IGF-1R. Both curcumin and thapsigargin inhibit the anchorage-independent growth of these three colon carcinoma cell lines. In conclusion, our findings indicate that curcumin inhibits PC zymogen maturation and consequently PC activity and that its inhibitory effect on Ca(2+) uptake into the ER allows and is sufficient to explain this phenomenon.

Topics: Animals; Caco-2 Cells; Calcium; Carcinoma; Cell Line, Tumor; CHO Cells; Colonic Neoplasms; Cricetinae; Curcumin; Endoplasmic Reticulum; HT29 Cells; Humans; Indoles; Proprotein Convertases; Receptor, IGF Type 1; Signal Transduction

The aim of the present study was to evaluate the antitumor effects of the curcumin analogue GL63 on radioresistant nasopharyngeal carcinoma (NPC) CNE2R cells and parental CNE2 cells. The cell viability and proliferation of NPC cells were detected by MTT assay and colony formation assay. The suppressive effect on tumor growth was examined using in vivo subcutaneously inoculated NPC tumor models using nude mice. The cell cycle distribution was detected using flow cytometry. Apoptosis was examined by Hoechst 33342 and Annexin V/PI staining assay. The protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP, were examined by western blotting. A growth inhibitory effect was observed following treatment with GL63 in a dose-dependent manner and was more potent when compared to curcumin. GL63 at 5 µM induced significant G2/M arrest and apoptosis in NPC. The tumor-suppressive activity of GL63 in NPC xenograft models was more potent when compared to curcumin. Furthermore, GL63 induced an ER stress response, upregulation of CHOP, XBP-1 and ATF-4 expression, while the same concentration of curcumin had no effect on ER stress. These results suggest that GL63 has more potent antitumor activity than curcumin, which is associated with activation of ER stress, induction of G2/M arrest and apoptosis in NPC cells.

Topics: Activating Transcription Factor 4; Animals; Antineoplastic Agents; Apoptosis; Bromobenzenes; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; DNA-Binding Proteins; Endoplasmic Reticulum Stress; Female; G2 Phase Cell Cycle Checkpoints; Humans; Mice; Mice, Nude; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Pentanones; Regulatory Factor X Transcription Factors; Transcription Factor CHOP; Transcription Factors; X-Box Binding Protein 1; Xenograft Model Antitumor Assays

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC.. NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting.. A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy.. Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC.

Topics: Apoptosis; Blotting, Western; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; COP9 Signalosome Complex; Curcumin; Flow Cytometry; Humans; Immunoblotting; Intracellular Signaling Peptides and Proteins; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Peptide Hydrolases; Radiation Tolerance; Radiation-Sensitizing Agents; RNA, Small Interfering; Transfection

Curcumin is a natural compound that exhibits a wide range of beneficial effects, among them the anti-tumor activity. Recently it was shown that curcumin may be efficient against drug resistant tumor cells. The goal of our investigation was to examine if human laryngeal carcinoma cells resistant to carboplatin display sensitivity to curcumin, as compared to parental cells, and if this sensitivity is altered, to determine the molecular mechanisms that are responsible for it. We found that carboplatin resistant 7T cells were also cross resistant to curcumin. After the treatment with equimolar concentration of curcumin, 7T cells exhibited lower intracellular accumulation of curcumin which coincided with reduced formation of reactive oxygen species (ROS), diminished lipid and DNA damage followed by reduced induction of apoptosis and expression of heat shock protein 70 (Hsp70), as compared to parental HEp-2 cells. However, after the treatment with equitoxic concentration of curcumin, intracellular accumulation and all the explored downstream effects were similar in both cell lines suggesting that resistance of 7T cells to curcumin was based on its reduced intracellular accumulation. Since curcumin accumulates mostly in the membranes, we explored the fatty acid composition of both cell lines, but we did not find any difference between them.

Topics: Antineoplastic Agents; Apoptosis; Carboplatin; Carcinoma; Cell Line, Tumor; Cell Survival; Curcumin; DNA Damage; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Fatty Acids; HSP70 Heat-Shock Proteins; Humans; Laryngeal Neoplasms; Lipid Peroxidation; Reactive Oxygen Species

Recently, many studies on health benefits associated with curcumin have been reported. In this study, the effects of curcumin on apoptosis of papillary thyroid cancer cell line K1 and its potential mechanisms were investigated. Curcumin was found to significantly inhibit cell viability and promoted cell apoptosis in a dose-dependent manner. Moreover, curcumin-induced cell apoptosis was characterized with a rapid stimulation of reactive oxygen species (ROS) production. Furthermore, curcumin-induced ROS generation led to the loss of mitochondrial membrane potential (MMP) and the disturbance of intracellular Ca(2+) concentration. A decrease in expression of Bcl-2 and the cleavage of poly ADP-ribose polymerase (PARP) were observed after exposure to curcumin. Results of this study may elucidate the curcumin-induced apoptosis effects on K1 cells. Thus, our results indicate a role of curcumin as health-promoting food ingredient, as well as a potential chemotherapeutic agent which is able to fight against papillary thyroid cancer.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma; Carcinoma, Papillary; Curcumin; Humans; Membrane Potential, Mitochondrial; Reactive Oxygen Species; Thyroid Cancer, Papillary; Thyroid Neoplasms

The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines, A2780 and CP70, induced by a novel curcumin analogue, B19. The proliferation of cells was detected with methyl thiazolyl tetrazolium (MTT) assay and apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) were assessed by the fluorescent indicator DCF-DA. The protein expression of the endoplasmic reticulum (ER) stress pathways, GRP78, XBP-1, ATF-4 and CHOP, was examined with Western blotting. A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin. At 20 µM, B19 induced significant apoptosis in CP70 cells. Furthermore, B19 induced the ER stress response, while curcumin had no effect on ER stress. These results suggest that B19 has more effective antitumor properties than curcumin, and is associated with the activation of ER stress and ROS in ovarian cancer cells.

Topics: Activating Transcription Factor 4; Apoptosis; Carcinoma; Cell Line, Tumor; Curcumin; DNA-Binding Proteins; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; Heat-Shock Proteins; Humans; Ketones; Ovarian Neoplasms; Reactive Oxygen Species; Receptors, G-Protein-Coupled; Regulatory Factor X Transcription Factors; Transcription Factor CHOP; Transcription Factors; X-Box Binding Protein 1

This study aimed to investigate the effect of Curcuma kwangsiensis polysaccharides on the viability of human nasopharyngeal carcinoma cell line CNE-2 cells, and explore the possible mechanisms. CNE-2 cells were treated with various concentrations of C. kwangsiensis polysaccharides, then the proliferation, apoptosis and the protein expression of apoptosis-related regulators p53 and Bcl-2 were assessed. The results demonstrated that C. kwangsiensis polysaccharides can significantly inhibit the proliferation of CNE-2 cells, which was possibly through the induction of apoptosis mediated by attenuating Bcl-2 expression and promoting p53 expression. The present study therefore indicates that C. kwangsiensis polysaccharides could be developed into potential drugs for nasopharyngeal carcinoma treatment.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma; Cell Line, Tumor; Curcuma; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Polysaccharides; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53

To study the molecular mechanisms of Curcuma Wenyujin extract-mediated inhibitory effects on human esophageal carcinoma cells.. The Curcuma Wenyujin extract was obtained by supercritical carbon dioxide extraction. TE-1 cells were divided into 4 groups after adherence. 100 microL RMPI-1640 culture medium containing 0.1% DMSO was added in Group 1 as the control group. 100 microL 25, 50, and 100 mg/L Curcuma Wenyujin extract complete culture medium was respectively added in the rest 3 groups as the low, middle, and high dose Curcuma Wenyujin extract groups. The effects of different doses of Curcuma Wenyujin extract (25, 50, and 100 mg/L) on the proliferation of human esophageal carcinoma cell line TE-1 in vitro were analyzed by MTT assay. The gene expression profile was identified by cDNA microarrays in esophageal carcinoma TE-1 cells exposed to Curcuma Wenyujin extract for 48 h. The differential expression genes were further analyzed by Gene Ontology function analysis.. Compared with the control group, MTT results showed that Curcuma Wenyujin extract significantly inhibited the proliferation of TE-1 cells in a dose-dependent manner (P<0.05). The expression level of 88 genes changed with significance, including 66 up-regulation genes and 22 down-regulation genes. Gene Ontology analysis indicated the genes coding for proteins was involved in signal transduction (6), cell cycle (8), apoptosis (14), and cell differentiation (10).. The Curcuma Wenyujin extract could inhibit the growth of human esophageal carcinoma cell line TE-1 in vitro. The molecular mechanisms might be associated with regulating genes expressions at multi-levels.

Topics: Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcuma; Esophageal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Plant Extracts; Transcriptome

Curcumin, a natural pigment from a traditional Chinese herb, has been attracting extensive attention. The present study aims to investigate cell death of nasopharyngeal carcinoma (NPC) cells induced by ultrasound sonication in the presence of curcumin in vitro.. The NPC cell line CNE2 was chosen as a tumor model, and curcumin concentration was kept constant at 10 µM while the cells were subjected to ultrasound exposure for 8 s at an intensity of 0.46 W/cm(2). Cell death was evaluated using flow cytometry with annexinV-FITC and propidium iodine staining, and nuclear staining with Hoechst 33258. Mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were analyzed using flow cytometry with rhodamine 123 and dichlorodihydrofluorecein diacetate staining.. Flow cytometry showed that the combination of ultrasound and curcumin significantly increased the necrotic or late apoptotic rate by up to 31.37% compared with the controls. Nuclear condensation was observed in the nuclear staining, and collapse of ΔΨm and ROS increase were found in the CNE2 cells after the treatment with curcumin and ultrasound.. The findings demonstrate that the presence of curcumin significantly enhances the ultrasound-induced cell death and ROS level, and induces the collapse of ΔΨm, suggesting that ultrasound sonication can increase the cell death of NPC cells in the presence of curcumin and that the treatment using curcumin and ultrasound together is a potential therapeutic modality in the management of malignant tumors.

Topics: Antineoplastic Agents; Carcinoma; Cell Death; Cell Line, Tumor; Combined Modality Therapy; Curcumin; Humans; Membrane Potential, Mitochondrial; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Reactive Oxygen Species; Ultrasonics

Activation of the Wingless (Wnt)/ß-catenin signaling pathway contributes to prostate tumorigenesis and metastasis. Depending of the stage of prostate cancer development, current drug therapies are of limited efficiency, so that prevention with natural compounds appears as an attractive strategy especially due to the slow progressive development of prostate cancer. We report here that the chemopreventive agent curcumin from the rhizome of Curcuma longa was able to affect cell proliferation of androgen-dependent prostate cancer through the induction of cell cycle arrest in G2 and modulation of Wnt signaling. Curcumin decreases the level of Tcf-4, CBP and p300 proteins implicated in the Wnt transcriptional complex that leads to the decrease of ß-catenin/Tcf-4 transcriptional activity and of the expression of ß-catenin target genes (cyclin D1 and c-myc). Subsequent cell death induction is linked to autophagy. Interestingly, in androgen-independent prostate cancer cells, curcumin does not affect Wnt/ß-catenin transcriptional activity. Altogether our results suggest that curcumin is an interesting chemopreventive agent for early stage prostate cancer.

Topics: Androgens; Antineoplastic Agents, Phytogenic; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Signal Transduction; Wnt Proteins

The functional interaction between integrin α6β4 and growth factor receptors has been implicated in key signaling pathways important for cancer cell function. However, few attempts have been made to selectively target this interaction for therapeutic intervention. Previous studies showed that curcumin, a yellow pigment isolated from turmeric, inhibits integrin α6β4 signaling important for breast carcinoma cell motility and invasion, but the mechanism is not currently known. To address this issue, we tested the hypothesis that curcumin inhibits the functional interaction between α6β4 and the epidermal growth factor receptor (EGFR). In this study, we found that curcumin disrupts functional and physical interactions between α6β4 and EGFR, and blocks α6β4/EGFR-dependent functions of carcinoma cells expressing the signaling competent form of α6β4. We further showed that curcumin inhibits EGF-dependent mobilization of α6β4 from hemidesmosomes to the leading edges of migrating cells such as lammelipodia and filopodia, and thereby prevents α6β4 distribution to lipid rafts where functional interactions between α6β4 and EGFR occur. These data suggest a novel paradigm in which curcumin inhibits α6β4 signaling and functions by altering intracellular localization of α6β4, thus preventing its association with signaling receptors such as EGFR.

Topics: Antineoplastic Agents; Carcinoma; Cell Line, Tumor; Curcumin; Epidermal Growth Factor; ErbB Receptors; Hemidesmosomes; Humans; Integrin alpha6beta4; Membrane Microdomains; Protein Binding; Protein Transport; Pseudopodia; Signal Transduction

Curcumin, a potent candidate anticancer agent, is a dietary pigment (phenolic compound) derived from the food flavoring spice turmeric (Curcuma longa), and it has been shown to have inhibitory effects on tumor cells through anti-proliferative and proapoptotic activities. However, there is no report showing curcumin-induced apoptotic cell death in human nasopharyngeal carcinoma cells in vitro. Thus, this study was performed to elucidate whether mitochondria and caspase cascades are involved in the modulation of apoptosis and cell cycle arrest in curcumin-treated NPC-TW 076 human nasopharyngeal carcinoma cells. The effects of curcumin on cell cycle arrest and apoptosis were measured by flow cytometry, and caspase-3 activity, apoptosis-associated protein levels and its regulated molecules were studied by flow cytometric assay and immunoblots. The results indicated that curcumin-induced G2/M phase arrest was associated with a marked decrease in the protein expression of cyclin A, cyclin B and cyclin-dependent kinase 1 (Cdk1). Curcumin-induced apoptosis was accompanied with upregulation of the protein expression of Bax and downregulation of the protein levels of Bcl-2, resulting in dysfunction of mitochondria and subsequently led to cytochrome c release and sequential activation of caspase-9 and caspase-3 in NPC-TW 076 cells in a time-dependent manner. These findings revealed that mitochondria, AIF caspase-3- dependent pathways play a vital role in curcumin-induced G2/M phase arrest and apoptosis of NPC-TW 076 cells in vitro.

Topics: Acetylcysteine; Antineoplastic Agents; Apoptosis; Calcium; Carcinoma; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Survival; Curcumin; Cytosol; DNA Damage; Enzyme Activation; Free Radical Scavengers; Humans; Membrane Potential, Mitochondrial; Mitochondria; Models, Biological; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Reactive Oxygen Species; Signal Transduction

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown.. Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH(+)/CD133(+)). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined.. Our results observed that ALDH(+)/CD133(+) colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model.. Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.

Topics: Animals; Antineoplastic Agents; Benzene Derivatives; Carcinoma; Cell Line, Tumor; Colonic Neoplasms; Curcumin; Drug Delivery Systems; Female; HCT116 Cells; HT29 Cells; Humans; Ketones; Mice; Mice, Inbred NOD; Mice, SCID; Neoplastic Stem Cells; Xenograft Model Antitumor Assays

Prostate-specific antigen (PSA) is a well-known marker for diagnosing and monitoring prostate cancer. Curcumin, a yellow curry pigment, has been reported to enhance androgen receptor (AR) degradation. We examined the effects of curcumin on increasing PSA expression by hypoxia and prolyl hydroxylase inhibitors, L-mimosine and dimethyloxalylglycine (DMOG), in human prostate carcinoma LNCaP cells.. The 3H-thymidine incorporation assay revealed that either L-mimosine or DMOG treatments attenuated cell proliferation. Immunoblot and enzyme-linked immunosorbent assays (ELISA) indicated that both L-mimosine and DMOG have an effect similar to hypoxia, which stabilized hypoxia-inducible factor-1α (HIF-1α) and induced PSA gene expression. The results of the immunoblot and transient gene expression assays indicated that induction of the PSA expression by hypoxia is both HIF-1α- and AR-dependent. Immunoblot assays revealed that a curcumin treatment (10 μM) decreased the protein abundance of AR but did not significantly affect the protein levels of HIF-1α and vascular endothelial growth factor, which were induced by hypoxia. ELISA and transient gene expression assays indicated that curcumin blocked the activation of L-mimosine or DMOG treatment on PSA expression.. These results indicate that curcumin blocked the enhanced effect of PSA expression by L-mimosine and DMOG that induce hypoxia condition.

Topics: Amino Acids, Dicarboxylic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Carcinoma; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Curcumin; Enzyme Inhibitors; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Iron Chelating Agents; Male; Mimosine; Neoplasm Proteins; Procollagen-Proline Dioxygenase; Prostate-Specific Antigen; Prostatic Neoplasms; Recombinant Proteins

Endometrial carcinoma is a malignant tumor in the uterus. Its current treatment is not satisfactory. The present study aimed to promote the inhibitory effect on the implanted endometrial tumor growth.. Nude mice were implanted with endometrial carcinoma. Some tumor-laden mice were treated with aromatase inhibitor letrozole and/or curcumin. The tumor growth was monitored. Tumor cell apoptosis was detected in both control and treated groups.. Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited the tumor growth; the inhibitor effect was further strengthened by combination with letrozole and curcumin. The results also showed that letrozole enhanced the expression of Bax and cytochrome c release and suppressed the expression of estrogen receptor in tumor cells. Treatment with curcumin inhibited the expression of Bcl-2 in tumor cells at the mRNA and protein levels. Tumor cell apoptosis was observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.. Treatment with either letrozole or curcumin could inhibit the xenografted endometrial tumor growth via inducing apoptosis in tumor cells. Combination of letrozole and curcumin further strengthened the inhibitory effect on tumor growth.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Carcinoma; Cell Line, Tumor; Cell Proliferation; Curcumin; Down-Regulation; Drug Synergism; Endometrial Neoplasms; Female; Humans; Letrozole; Mice; Mice, Inbred BALB C; Mice, Nude; Nitriles; Triazoles; Xenograft Model Antitumor Assays

Elemene is a chemical extracted from plants. It has demonstrated anti-tumour capability. Although widely studied, there has been little reported regarding its tissue distribution. Our aim was to rectify this.. The tissue distribution of elemene was studied after intragastric or intravenous administration in rats. The effectiveness of elemene in treating brain tumours was studied using the G-422 tumour cell model in mice.. Elemene had a higher concentration in the lungs, spleen and livers than other tissues of normal rats after intragastric and intravenous administration, while the concentration in the gastrointestinal tract was greater after intragastric administration. Elemene molecules were also detected in the rats' brain tissue. Elemene had a therapeutic effect on mice inoculated with G-422 cells both intracranially and subcutaneously. The best life-extending rate and the best tumour-inhibiting rate of elemene were 64.43% and 34.46%, respectively, when 80 mg/kg elemene was used for treatment.. The results from the tissue distribution study showed that elemene can pass through the blood-brain barrier. The therapeutic experiments showed that elemene is effective in treating cerebral malignancy.

Topics: Animals; Antineoplastic Agents, Phytogenic; Blood-Brain Barrier; Brain; Brain Neoplasms; Carcinoma; Cell Line, Tumor; Curcuma; Gastrointestinal Tract; Humans; Liver; Lung; Mice; Mice, Nude; Models, Animal; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Spleen; Tissue Distribution; Xenograft Model Antitumor Assays

We have recently shown that macrophage-stimulating protein (MSP) promotes the invasion of recepteur d'origine nantais (RON), a tyrosine kinase receptor-positive MDA-MB-231, MDA-MB-468 breast cancer cells, and also identified the regulatory elements required for RON gene expression. In this report, we have analyzed the efficacy of a chemopreventive agent, curcumin, in blocking RON tyrosine kinase-mediated invasion of breast cancer cells. Reverse transcription-PCR and Western analysis indicated the down-regulation of the RON message and protein, respectively, in MDA-MB-231 and MDA-MB-468 cells. Significantly, curcumin-mediated inhibition of RON expression resulted in the blockade of RON ligand, MSP-induced invasion of breast cancer cells. We have identified two putative nuclear factor-kappaB p65 subunit binding sites on the RON promoter. Using chromatin immunoprecipitation analysis and site-directed mutagenesis of the RON promoter, we have confirmed the binding of p65 to the RON promoter. Our data show that curcumin reduces RON expression by affecting p65 protein expression and transcriptional activity. Treatment of MDA-MB-231 cells with pyrrolidine dithiocarbamate, an inhibitor of p65, or small interfering RNA knockdown of p65, blocked RON gene expression and MSP-mediated invasion of MDA-MB-231 cells. This is the first report showing the regulation of human RON gene expression by nuclear factor-kappaB and suggests a potential therapeutic role for curcumin in blocking RON tyrosine kinase-mediated invasion of carcinoma cells.

Topics: Binding Sites; Breast Neoplasms; Carcinoma; Curcumin; Down-Regulation; Drug Evaluation, Preclinical; Gene Expression Regulation, Neoplastic; Humans; Mutation; Neoplasm Invasiveness; NF-kappa B; Promoter Regions, Genetic; Protein Binding; Protein-Tyrosine Kinases; Receptor Protein-Tyrosine Kinases; RNA, Messenger; RNA, Small Interfering; Transfection; Tumor Cells, Cultured

Curcumin, a polyphenol natural product isolated from the rhizome of the plant Curcuma longa, has emerged as a promising anticancer therapeutic agent. However, the mechanism by which curcumin inhibits cancer cell functions such as cell growth, survival, and cell motility is largely unknown. We explored whether curcumin affects the function of integrin alpha(6)beta(4), a laminin adhesion receptor with an established role in invasion and migration of cancer cells. Here we show that curcumin significantly reduced alpha(6)beta(4)-dependent breast cancer cell motility and invasion in a concentration-dependent manner without affecting apoptosis in MDA-MB-435/beta4 (beta(4)-integrin transfectants) and MDA-MB-231 breast cancer cell lines. Further, curcumin selectively reduced the basal phosphorylation of beta(4) integrin (Y1494), which has been reported to be essential in mediating alpha(6)beta(4)-dependent phosphatidylinositol 3-kinase activation and cell motility. Consistent with this finding, curcumin also blocked alpha(6)beta(4)-dependent Akt activation and expression of the cell motility-promoting factor ENPP2 in MDA-MB-435/beta4 cell line. A multimodality approach using curcumin in combination with other pharmacologic inhibitors of alpha(6)beta(4) signaling pathways showed an additive effect to block breast cancer cell motility and invasion. Taken together, these findings show that curcumin inhibits breast cancer cell motility and invasion by directly inhibiting the function of alpha(6)beta(4) integrin, and suggest that curcumin can serve as an effective therapeutic agent in tumors that overexpress alpha(6)beta(4).

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Breast Neoplasms; Carcinoma; Cell Adhesion; Cell Movement; Curcumin; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Enzyme Inhibitors; Humans; Indoles; Integrin alpha6beta4; Neoplasm Invasiveness; Oncogene Protein v-akt; Phosphorylation; Piperazines; Signal Transduction; Sulfonamides; Tumor Cells, Cultured

Curcumin, a component of turmeric, has been shown to suppress inflammation and angiogenesis largely by inhibiting the transcription factor nuclear factor-kappaB (NF-kappaB). This study evaluates the effects of curcumin on ovarian cancer growth using an orthotopic murine model of ovarian cancer.. In vitro and in vivo experiments of curcumin with and without docetaxel were done using human ovarian cancer cell lines SKOV3ip1, HeyA8, and HeyA8-MDR in athymic mice. NF-kappaB modulation was ascertained using electrophoretic mobility shift assay. Evaluation of angiogenic cytokines, cellular proliferation (proliferating cell nuclear antigen), angiogenesis (CD31), and apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) was done using immunohistochemical analyses.. Curcumin inhibited inducible NF-kappaB activation and suppressed proliferation in vitro. In vivo dose-finding experiments revealed that 500 mg/kg orally was the optimal dose needed to suppress NF-kappaB and signal transducers and activators of transcription 3 activation and decrease angiogenic cytokine expression. In the SKOV3ip1 and HeyA8 in vivo models, curcumin alone resulted in 49% (P = 0.08) and 55% (P = 0.01) reductions in mean tumor growth compared with controls, whereas when combined with docetaxel elicited 96% (P < 0.001) and 77% reductions in mean tumor growth compared with controls. In mice with multidrug-resistant HeyA8-MDR tumors, treatment with curcumin alone and combined with docetaxel resulted in significant 47% and 58% reductions in tumor growth, respectively (P = 0.05). In SKOV3ip1 and HeyA8 tumors, curcumin alone and with docetaxel decreased both proliferation (P < 0.001) and microvessel density (P < 0.001) and increased tumor cell apoptosis (P < 0.05).. Based on significant efficacy in preclinical models, curcumin-based therapies may be attractive in patients with ovarian carcinoma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Curcumin; Disease Models, Animal; Female; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic; NF-kappa B; Ovarian Neoplasms; Platelet Endothelial Cell Adhesion Molecule-1

Photodynamic treatment (PDT) can elicit a diverse range of cellular responses, including apoptotic cell death. Previously, we showed that PDT stimulates caspase-3 activation and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. Curcumin, the yellow pigment of Curcuma longa, is known to have anti-oxidant and anti-inflammatory properties. In the present study, using Rose Bengal (RB) as the photosensitizer, we investigated the effect of curcumin on PDT-induced apoptotic events in human epidermal carcinoma A431 cells. We report that curcumin prevented PDT-induced JNK activation, mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PAK2. Using the cell permeable dye DCF-DA as an indicator of reactive oxygen species (ROS) generation, we found that both curcumin and ROS scavengers (i.e., l-histidine, a-tocopherol, mannitol) abolished PDT-stimulated intracellular oxidative stress. Moreover, all these PDT-induced apoptotic changes in cells could be blocked by singlet oxygen scavengers (i.e., l-histidine, a-tocopherol), but were not affected by the hydroxyl radical scavenger mannitol. In addition, we found that SP600125, a JNK-specific inhibitor, reduced PDT-induced JNK activation as well as caspase-3 activation, indicating that JNK activity is required for PDT-induced caspase activation. Collectively, these results demonstrate that singlet oxygen triggers JNK activation, cytochrome c release, caspase activation and subsequent apoptotic biochemical changes during PDT and show that curcumin is a potent inhibitor for this process.

Topics: alpha-Tocopherol; Apoptosis; Carcinoma; Caspase 3; Caspase Inhibitors; Caspases; Cell Line, Tumor; Curcumin; Cytochromes c; Enzyme Activation; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases; Oxidative Stress; p21-Activated Kinases; Photochemotherapy; Poly(ADP-ribose) Polymerases; Protein Serine-Threonine Kinases; Reactive Oxygen Species

In our study, we present experimental evidence suggesting that curcumin exerts multiple different suppressive effects on human breast carcinoma cells in vitro. Our experiments demonstrate that curcumin's antiproliferative effects are estrogen dependent in ER (estrogen receptor)-positive MCF-7 cells, being more pronounced in estrogen-containing media and in the presence of exogenous 17-beta estradiol. Curcumin inhibits the expression of ER downstream genes including pS2 and TGF-beta (transforming growth factor) in ER-positive MCF-7 cells, and this inhibition is also dependent on the presence of estrogen. Curcumin also decreases ERE (estrogen responsive element)-CAT activities induced by 17-beta estradiol. In addition, we demonstrate that curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells. These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. Our study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231 cells.

Topics: Antineoplastic Agents; Breast Neoplasms; Carcinoma; Cell Division; Curcumin; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Dose-Response Relationship, Drug; Estrogen Antagonists; Female; Humans; Neoplasm Invasiveness; Neovascularization, Pathologic; Proteins; Receptors, Estrogen; Response Elements; RNA, Neoplasm; Transcription, Genetic; Transforming Growth Factor alpha; Trefoil Factor-1; Tumor Cells, Cultured; Tumor Suppressor Proteins