curcumin and Lymphoma

Emerging evidence suggests that natural plant ingredients have played an important role in the healthcare of many countries. Several of these natural plant products possess therapeutic potential for various diseases including cancer. Curcumin is the pigment of turmeric, a well-known chemopreventive agent that has been shown to suppress the proliferation of a wide variety of tumor cells, including lymphoma. Curcumin has been shown to have cancer chemopreventive potential against a variety of tumors via targeting key survival pathways that are aberrantly activated in cancer cells.. This review discusses therapeutic potential of curcumin in malignancies of lymphoma as well as therapeutic implications of the recent advances in the field.. Dietary-compound curcumin hardwires to multiple cellular processes. Suppression of cell proliferation, induction of apoptosis, and inhibition of metastasis are considered to be the major mechanisms underlying its anticancer properties.

Topics: Animals; Antineoplastic Agents; Curcumin; Drug Discovery; Humans; Lymphoma

Although traditional medicines have been used for thousands of years, for most such medicines neither the active component nor their molecular targets have been very well identified. Curcumin, a yellow component of turmeric or curry powder, however, is an exception. Although inhibitors of cyclooxygenase-2, HER2, tumor necrosis factor, EGFR, Bcr-abl, proteosome, and vascular endothelial cell growth factor have been approved for human use by the United States Food and Drug Administration (FDA), curcumin as a single agent can down-regulate all these targets. Curcumin can also activate apoptosis, down-regulate cell survival gene products, and up-regulate p53, p21, and p27. Although curcumin is poorly absorbed after ingestion, multiple studies have suggested that even low levels of physiologically achievable concentrations of curcumin may be sufficient for its chemopreventive and chemotherapeutic activity. Thus, curcumin regulates multiple targets (multitargeted therapy), which is needed for treatment of most diseases, and it is inexpensive and has been found to be safe in human clinical trials. The present article reviews the key molecular mechanisms of curcumin action and compares this to some of the single-targeted therapies currently available for human cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Biological Availability; Breast Neoplasms; Cell Division; Cell Line, Tumor; Cell Survival; Curcumin; Humans; Lymphoma; Models, Animal; Neoplasm Metastasis; Spices; United States; United States Food and Drug Administration

Despite the role of curcumin in controlling inflammation, angiogenesis, and cancer in human cells, its therapeutic use is limited. The reasons are quick metabolic breakdown, low aqueous solubility, and bioavailability. This study describes the advantages of clinical-grade curcumin-incorporated fibrin matrix either in lyophilized off-the-shelf wafer or injectable hydrogel forms, as a biodegradable local delivery system. To produce the curcumin-fibrin wafer, used clinical-grade fibrin sealant in a modified composition. To fabricate wafer, we premixed the curcumin with either fibrinogen or thrombin, before clotting into a hydrogel. Sustained release of active curcumin from fibrin wafer, suspended in culture medium at 37 °C lasted for seven days. Upon premixing albumin with thrombin and subsequently adding curcumin into the mixture improved the loading concentration and stability. Dose- and time-dependent apoptotic function of curcumin on cancer cell lines upon release from fibrin wafer, were demonstrated in vitro. In vivo immuno-modulation and a nontoxic response to curcumin released from fibrin into the peritoneal cavity of mice were established. The cytotoxic effect of released curcumin was demonstrated; showing both a preventive and therapeutic role against tumor growth. In vivo studies used Dalton's Lymphoma Ascites (DLA) mice model. Both implanted fibrin wafer and injected hydrogel can breakdown by a physiological process and get cleared by the fibrinolytic mechanism. The lyophilized fibrin wafer could function as a hemostat, adhere to surgical cancer tissues, and arrest bleeding. The potential of curcumin in preventing solid tumor metastasis may be explored upon the sustained delivery of the molecule from the fibrin wafer.

Topics: A549 Cells; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Ascites; Cell Proliferation; Curcumin; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Liberation; Female; Fibrin; Humans; Hydrogels; Lymphoma; Mice; PC-3 Cells

Topics: Animals; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Cadherins; Caspase 3; Caspase 9; Cell Line, Tumor; Cell Proliferation; Cephalotaxus; Curcuma; Curcumin; Drug Therapy, Combination; Homoharringtonine; Lymphoma; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Phytotherapy; Plant Extracts; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta; Xenograft Model Antitumor Assays

The traditional chemotherapy, including Adriamycin (Doxorubicin, DOX), is widely used and is part of the first-line chemotherapy of invasive B cell lymphoma. DOX is nonselective cytotoxic drug and has many adverse effects, which limit its clinical application in combination with other anti-cancer drugs. Optimization of the delivery system targeting tumor microenvironment could be a feasible approach that may have significant clinical significance. Further, combination of DOX with other anticancer drugs, such as curcumin, can enhance the synergistic effects, possibly through epigenetic mechanisms. Hence, we evaluated the efficacy and toxicity of novel nanoparticles that enable the co-delivery of DOX and curcumin in the treatment of invasive B cell lymphoma both in vivo and vitro. The polymer nano materials [mPEG-b-P(Glu-co-Phe)] was used to co-load DOX and curcumin (CUR): L-DOX + CUR. DOX signal was measured to determine the ability of the drugs entering the cells by flow cytometry, and the different enrichment areas in the cells were directly observed by confocal microscope. The toxicity of LDOX + CUR was tested by CCK-8 assay in different cells, and the synergistic coefficients were calculated. The cell apoptosis and the possible mechanisms of apoptosis pathways regulation by L-DOX + CUR were examined using flow cytometry and Western Blot. The MTD (maximum tolerable dose) test was performed in mice. Tumor-bearing SCID mice (i.e., BJAB cell) were used to evaluate the in vivo efficacy of L-DOX + CUR. L-DOX + CUR, was prepared successfully, and the mole ratio of DOX and CUR fixed in 1.0:1.2. (DOX loading rate 9.7%, CUR loading rate 8.1%). L-DOX + CUR exhibited increased intracellular delivery and the main enrichment area of DOX was nucleus. L-DOX + CUR increased cytotoxicity, induced higher rates of apoptosis, and had synergistic effect, especially in BJAB cells (min CI 0.019). It even had epigenetic effect and affected miRNA levels favorably by down-regulating miR-21, miR-199a and up-regulating miR-98 and miR-200c. Additionally, L-DOX + CUR increased MTD in Kunming mice (i.e., 25 mg/kg), compared to DOX (10 mg/kg) and L-DOX (20 mg/kg). In BJAB cell bearing SCID mice, L-DOX + CUR treatment suppressed tumor growth compared to DOX or L-DOX alone, and exhibited less weight loss in mice. We developed new polymer nanoparticles-mPEG-b-P (Glu-co-Phe) co-loaded with DOX and DUR. L-DOX + CUR exhibited synergistic cytotoxic and apoptotic effects on invasive B cell ly

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Doxorubicin; Drug Carriers; Drug Synergism; Endocytosis; Humans; Intracellular Space; Lymphoma; Male; Mice; Nanostructures; Peptides; Polyethylene Glycols; Xenograft Model Antitumor Assays

Curcumin is a natural compound isolated from the rhizome of Curcuma longa. It possesses anti-tumor activity through arresting cell cycles and promoting cell apoptosis. However, the effect of curcumin on DNA damage is not well defined. In this study, we investigated the effect of curcumin on inducing DNA damage and on sensitizing lymphoma cells to anti-tumoral DNA damage drugs. Western blot showed curcumin induced γ-H2AX foci in CH12F3 lymphoma cells, which suggests curcumin induces DNA breaks. In addition, curcumin decreased the expression of Rad51, which suggests curcumin induces DNA damage through regulating Rad51-dependant homologous recombination. Rad51-dependant homologous recombination is a vital DNA repair pathway for cancer cells to resist anti-tumoral DNA damage drugs, therefore, we studied the effect of curcumin on the sensitizing lymphoma cells to various chemotherapeutic drugs. We found low level of curcumin (5μM) sensitized lymphoma cells to anti-tumoral DNA damage agents including cisplatin, methyl methanesulfonate, hydroxyurea and camptothecin. We also found curcumin sensitized CH12F3 lymphoma cells to DNA-PK and PARP inhibitors. Flow cytometry analysis showed curcumin promoted apoptosis and western blot analysis confirmed curcumin activated caspase3-dependent apoptosis. Taken together, these results demonstrate that curcumin induces DNA damage through regulating Rad51-dependant homologous recombination and triggers caspase3-dependent apoptosis, more importantly, curcumin sensitizes lymphoma cells to various DNA damage drugs. Consequently, curcumin would be a potent agent for sensitizing lymphoma cells to anti-tumoral chemotherapeutic agents.

Topics: Animals; Cell Line, Tumor; Cell Survival; Curcumin; DNA Damage; Dose-Response Relationship, Drug; Homologous Recombination; Lymphoma; Mice; Rad51 Recombinase

Warburg effect is characterized by the upregulation of HIF-1 and c-Myc regulated LDH-A, even aerobically owing to hypoxic environment and alterations in oncogenes or tumor suppressor genes in cancer. Reduced antioxidant defence system in transformed cells favors higher ROS production, which plays a significant role in carcinogenesis and acts as an important regulator of NF-κB. In addition, various proinflammatory cytokines play active roles in maintenance and progression of cancer.. In continuation with our previous studies illustrating the long-term effect of curcumin using a liver tissue, present study was aimed to elucidate the anti-cancer effect of curcumin due to its long-term effect in the regulation of glycolytic metabolism, NF-κB activation, expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.. Spectrophotometric assays, RT-PCR and EMSA were performed to address the problems.. Results revealed that curcumin-induced activation of antioxidant enzymes, Nrf2 and downstream signaling gene NQO1. Reduction of oxidative stress, down-regulation of NADPH: Oxidase, decline in ROS and H2O2 levels were also observed. Activation of NF-κB, expression of COX2, HIF-1α and cMyc, as well as expression and activity of LDH-A were significantly reduced by curcumin. Besides, expression of proinflammatory cytokines was significantly down-regulated via reducing binding of nuclear protein with AP-1, NF-IL6, ETS and NF-κB binding elements of IL-1α, IL-1β, TNF-α and IL-6 promoters, respectively.. Curcumin downregulates glycolytic metabolism via modulation of stress-activated genes and reduces oxidative stress by enhancing antioxidant defence system, which inhibits activation of NF-κB signaling and expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.

Topics: Animals; Antineoplastic Agents; Ascites; Curcumin; Cytokines; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Glucose; Glycolysis; Inflammation; Lymphoma; Male; Mice; Mice, Inbred AKR; Mice, Inbred DBA; Molecular Structure; NF-E2-Related Factor 2; Structure-Activity Relationship

Curcumin is a yellow polyphenolic chemopreventive agent isolated from the rhizomes of Curcuma longa. It is approved as Generally Regarded as Safe by US FDA. Nonetheless, its clinical success is limited due to its poor aqueous solubility, fast metabolism and short biological half-life attributes.. Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to overcome these biopharmaceutical drawbacks.. Curcumin liposomes with/without quercetin were prepared by lipid hydration technique. The liposomes were characterized for their particle size, zeta potential, surface morphology, drug loading and release characteristics. The toxicity of the liposomes were evaluated in-vitro and their invivo efficacy were tested against Dalton's ascites lymphoma in mice.. Liposomes designed showed particle size of 261.8 ± 2.1 nm with a negative zeta potential of -22.6±1.6 mV. Quercetin decorated liposomes were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to those without quercetin. Similarly, the presence of quercetin also contributed to enhanced cytotoxicity of the liposomal formulation towards HT-29 cells and HCT-15 cells.. Newer liposomal design exhibited promising potential to emerge as alternative anticancer therapeutics.

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Curcumin; Drug Screening Assays, Antitumor; HT29 Cells; Humans; Liposomes; Lymphoma; Male; Mice; Neoplasms, Experimental; Particle Size; Quercetin; Surface Properties; Tumor Cells, Cultured

Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. The current study aimed to prove the safe use of the Curc-Alb conjugate in animals and to demonstrate that it retains drug action both in vitro and in vivo. Dalton's lymphoma ascites (DLA) cell viability was inhibited by the Curc-Alb conjugate in a dose dependent manner in vitro, as evidenced by the MTT assay. Administration of up to 11.4 mg of conjugated curcumin per kg body weight to healthy animals was non-toxic both in terms of lethality and weight loss. Histological analysis of vital organs (kidney, liver and spleen) also did not show toxic effects. Favorable immuno-modulatory activity was observed after continuous administration of sub-acute doses of the conjugate which caused increase in total leukocyte count, platelet count, and viable cell count in bone marrow, and enhanced proliferation of lymphocyte in vitro upon culture. In vivo studies in the DLA tumor model in mice demonstrated that conjugated drug induces tumor reduction and prevention. Significant tumor reduction was observed when the Curc-Alb conjugate was administered intraperitoneally in DLA-induced mice after 1 day (prevention therapy) and 7 days (reduction therapy) of tumor induction. There was significant reduction in both tumor volume and tumor cell numbers in the treated animals as well as a marked increase in their mean survival time and percent increase in life span. The effect was greater when the conjugate was administered soon after inducing the tumor as compared to when treatment was started after allowing tumor to grow for 7 days. Thus, the results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties. The study postulates the drug form has the potential to be used as an anticancer agent in affected human subjects.

Topics: Albumins; Animals; Anticarcinogenic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Humans; Immunomodulation; Lymphoma; Male; Mice; Solubility; Tumor Burden

Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are typical multifunctional proinflammatory cytokines involved actively in the regulation of immunity, hematopoiesis, inflammation and carcinogenesis. Coordinated regulation of these cytokines could be required for effective regulation of early phase inflammation and cancer progression. The present work was aimed to analyze the anti-carcinogenic action of curcumin on the expression of TNF-α and IL-6 even after withdrawal of treatment. Up-regulated expressions of TNF-α and IL-6 in terms of mRNA and protein levels in lymphoma bearing mice were significantly down-regulated by curcumin as compared to normal. Electrophoretic mobility shift assay (EMSA) results revealed that curcumin reduced binding of nuclear protein with ETS and NF-κB binding elements of TNF-α and IL-6 promoters, respectively. The anti-carcinogenic effect of curcumin against lymphoma progression has been reported previously. In continuation, the present study suggests that the long-term effect of curcumin may contribute to attenuate cancer progression via the down-regulation of TNF-α and IL-6 modulated by E26 transformation-specific protein (ETS) and nuclear factor-κB (NF-κB), respectively.

Topics: Animals; Antineoplastic Agents; Blotting, Western; Curcumin; Disease Progression; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation, Neoplastic; Interleukin-6; Lymphoma; Mice, Inbred AKR; NF-kappa B; Promoter Regions, Genetic; Protein Binding; Proto-Oncogene Protein c-ets-1; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Time Factors; Tumor Necrosis Factor-alpha

NF-κB (nuclear factor κB) plays a significant role in inflammation, immunity, cell proliferation, apoptosis and malignancy. ROS (reactive oxygen species) are among the most important regulating factors of NF-κB. Intracellular ROS are mainly regulated by an endogenous antioxidant defence system. Any disruption of redox balance leads to oxidative stress, which causes a number of pathological conditions including inflammation and malignancy. Increased metabolic activity in cancerous cells leads to oxidative stress, which is further enhanced due to depletion of the endogenous antioxidant defence system. However, the activation and signalling of NF-κB are reported to be inhibited by overexpression and induced activity of antioxidant enzymes. Therefore the present study focuses on the correlation between the endogenous antioxidant defence system, ROS and NF-κB activation during lymphoma growth in mice. The study highlights the anti-carcinogenic role of curcumin by modulation of NF-κB activation and oxidative stress via the endogenous antioxidant defence system. Oxidative stress was monitored by lipid peroxidation, protein carbonylation and antioxidant enzyme activity. NF-κB-mediated signalling was tested by DNA-binding activity. The results reflect that intracellular production of H2O2 in oxidative tumour micro-environment regulates NF-κB activation. Curcumin inhibits oxidative state in the liver of lymphoma-bearing mice by enhancing the transcription and activities of antioxidant enzymes, which in turn modulate activation of NF-κB, leading to a decrease in lymphoma growth. Morphological changes as well as cell proliferation and cell survival assays confirmed reduced lymphoma growth. Thus curcumin contributes to cancer prevention by disrupting the vicious cycle of constant ROS production, responsible for a high oxidative micro-environment for tumour growth.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Curcumin; Lipid Peroxidation; Lymphoma; Male; Mice; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Signal Transduction

Cancer metastasis involves multiple processes which may complicate clinical management and even lead to death. Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion, metastasis and angiogenesis, depending on whether agents can inhibit MMPs which could lead to inhibition of the migration and invasion of cancer cells. Curcumin, the active constituent of the dietary spice turmeric, has potential for the prevention and therapy of cancer. However, there is no study to address the effects of curcumin on migration and invasion of mouse-rat hybrid retina ganglion cells (N18). This is the first study to explore the anti-migration and -invasion of curcumin in mouse-rat hybrid retina ganglion cells (N18) in vitro. Curcumin exerted a dose- and time-dependent inhibitory effect on the invasion and migration of N18 cells in vitro. Results from Western blotting showed that curcumin inhibited the protein levels of PKC, FAK, NF-kappaB p65 and Rho A leading to the inhibition of ERK1/2, MKK7, COX-2 and ROCK1, respectively, finally causing the inhibition of MMP-2 and -9 for the inhibition of migration and invasion of N18 cells. Moreover, this action was involved in the inhibition of gene expression of MMP-2 and -7, FAK, ROCK1 and Rho A. Overall, the above data show that the anticancer effect of curcumin also exists for the inhibition of migration and invasion in N18 cells, and that curcumin may be a powerful candidate for developing preventive agents for cancer metastasis.

Topics: Animals; Antineoplastic Agents; Cell Movement; Curcumin; Focal Adhesion Protein-Tyrosine Kinases; Hybrid Cells; Lymphoma; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Neoplasm Invasiveness; Rats; Retinal Ganglion Cells; rho-Associated Kinases; rhoA GTP-Binding Protein; RNA, Messenger

A variety of cancers ectopically express human chorionic gonadotropin beta (hCGbeta). Patients harboring such cancers have poor prognosis and adverse survival. A recombinant chimeric antibody, cPiPP, exhibiting high affinity and specificity for hCGbeta/hCG was engineered. This study was designed to determine whether this antibody alone or conjugated to curcumin can selectively kill tumor cells expressing hCGbeta.. The study was carried out on MOLT-4 and U-937 cells expressing hCGbeta and on peripheral blood leukocytes of acute myeloid leukemia (AML) patients. The anticancerous compound curcumin was conjugated to cPiPP. The binding of cPiPP and cPiPP-curcumin conjugate to cells was studied by flow cytometry and cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), FACS with propidium iodide staining, trypan blue exclusion assay and microscopy.. The antibody did not impair the growth of MOLT-4 and U-937 cells in culture. Its conjugate with curcumin, however, was lethal to both cell lines. The immunoconjugate killed tumor cells bearing the CD33 marker of an AML patient expressing hCGbeta but did not have a similar action on cells of another AML patient with the CD13 marker but who was negative for hCGbeta.. A humanized antibody against hCGbeta linked to curcumin has potential for therapy of hCGbeta-expressing tumors.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Separation; Chorionic Gonadotropin, beta Subunit, Human; Curcumin; Drug Design; Female; Humans; Leukemia; Leukemia, Myeloid, Acute; Leukocytes, Mononuclear; Lymphoma; Male; Middle Aged; Sialic Acid Binding Ig-like Lectin 3; Tetrazolium Salts; Thiazoles; U937 Cells

Previous reports from our laboratory have shown that in Swiss female mice exposed to an acute dose (3 Gy) of whole body irradiation (WBI), induced thymic lymphoma (TL) resulted after three to four weeks of exposure. The present study was aimed to further evaluate dependency on gender and effect of age of mice at the time of irradiation on TL incidence. A significant decrease in body weight gain was observed in female mice exposed to WBI, which was found to be correlated with the increase in weight and size of thymus, compared to their respective controls. An increase in TL incidence was observed with the increased postirradiation time, which was 47, 80, and 93% after 90, 120, and 150 days of WBI, respectively, in female mice. In irradiated female mice, the TL incidence was significantly higher and the growth of tumor in terms of weight and size was more aggressive than in males of the same age. Moreover, mice with higher age groups at the time of irradiation showed substantial decrease in TL incidence and its aggressiveness; and these effects were more conspicuous in males than in females. In mice irradiated at the age group of three to four weeks, the TL incidence was 83 and 72% in female and male, respectively, which was decreased to 74% in female and 14% in male in the age group of 12-13 weeks. It was further observed that the postirradiation feeding of animals with antioxidants resulted in a significant decrease in TL incidence, and the prevention in TL incidence was more in animals fed with curcumin (55%) than with ascorbic acid and eugenol (20%). These results have provided significant new findings on the phenomenon of radiation-induced TL incidence related to gender and age at the time of irradiation and its prevention by postirradiation antioxidant feeding to mice.

Topics: Aging; Animals; Antioxidants; Ascorbic Acid; Body Weight; Curcumin; Eugenol; Female; Gamma Rays; Lymphoma; Male; Mice; Neoplasms, Radiation-Induced; Organ Size; Sex Factors; Thymus Gland; Thymus Neoplasms; Whole-Body Irradiation

Curcumin, a lipid soluble antioxidant, exhibits solvent and medium sensitive absorption and fluorescence properties. Using such changes, the average binding constants of curcumin to phosphatidylcholine (PC) liposomes and human serum albumin (HSA) were estimated to be 2.5 x 10(4) M(-1) and 6.1 x 10(4) M(-1) respectively. From the studies on temperature dependent fluorescence anisotropy of liposomal curcumin and its fluorescence quenching by acrylamide and iodide, it was concluded that curcumin is located in the gel phase of the liposomes. Similarly from the studies on quenching of tryptophan fluorescence in HSA by curcumin, it was found to be in the same domain as that of tryptophan. Both liposomal and HSA vehicles were examined for the transfer of curcumin to spleen lymphocyte cells, EL4 lymphoma cell line and compared with aqueous DMSO vehicles. From these studies it was found that liposomal vehicle is capable of loading more curcumin in to cells than HSA or aqueous-DMSO, and lymphoma cells show preferential uptake of curcumin to lymphocytes. The fluorescence of curcumin in EL4 lymphoma cells was found to be significantly higher as compared to the lymphocytes. The present study demonstrates a simple and quantitative method of estimation of curcumin delivered to cells by different vehicles using absorption and fluorescence spectroscopy.

Topics: Absorption; Animals; Cell Line, Tumor; Curcumin; Fluorescence Polarization; Humans; Liposomes; Lymphocytes; Lymphoma; Mice; Phosphatidylcholines; Serum Albumin; Spectrometry, Fluorescence

The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3.

Topics: Antineoplastic Agents; Apoptosis; Caspase 3; Caspases; Cell Proliferation; Curcumin; Cytochromes c; DNA-Binding Proteins; Enzyme Activation; Humans; Janus Kinase 1; Lymphoma; Membrane Potentials; Mitochondria; Pleural Effusion, Malignant; Poly(ADP-ribose) Polymerases; Protein-Tyrosine Kinases; Signal Transduction; STAT3 Transcription Factor; Trans-Activators; Tumor Cells, Cultured

Curcumin is a crucial component of curcuma. Recently more attention has been paid to the effect of curcumin on specific proliferative inhibition and inducing apoptosis of tumor cells. This study was aimed to investigate the anticancer activities of curcumin and its molecular mechanism. Raji cells (lymphoma cell line) were selected as studying targets, peripheral blood mononuclear cells (PBMNC) obtained from healthy donors were separated by Ficoll solution and suspended in RMPI 1640. The inhibition rates of Raji cells and PBMNC after treatment with curcumin at various concentrations and different times were determined by MTT method and were compared. The expressions of caspase 8 and caspase 9 in Raji cells after treatment with curcumin at 25 micromol/L (IC(50)) and for 24 hours were detected by Western blot. The results showed that curcumin could inhibit proliferation of Raji cells in dose-and time-dependent manner. Curcumin could remarkablely enhance the Raji cell apoptosis at 25 micromol/L and 24 hours (P < 0.01), and its effect was dose-dependent and time-selective. Curcumin had no remarkable effect on PBMNC at certain concentrations, which demonstrated that curcumin could selectively inhibit tumor cell proliferation. It is concluded that the expression of caspase 8 and caspase 9 plays an important role in the proliferation and apoptosis of Raji cells, so that curcumin showed inhibitive effect on Raji cells at various concentrations.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Blotting, Western; Caspase 8; Caspase 9; Cell Line, Tumor; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Humans; Inhibitory Concentration 50; Lymphoma

Female Sencar mice (6 weeks old) were administered 1 mg of 7,12-dimethylbenz[a]anthracene (DMBA) by oral gavage once a week for 5 weeks. At 20 weeks after the first dose of DMBA, 68% of mice developed mammary tumors (the average 1.08 tumors per mouse) and 45% had lymphomas/leukemias. Feeding 1% dibenzoylmethane (DBM) in AIN 76A diet, starting at 2 weeks before the first dose of DMBA and continuing until the end of the experiment, inhibited both the multiplicity and incidence of DMBA-induced mammary tumor by 97%. The incidence of lymphomas/leukemias was completely inhibited by 1% DBM diet. In contrast, feeding 2% curcumin diet had little or no effect on the incidence of mammary tumors, and the incidence of lymphomas/leukemias was reduced by 53%.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Benzoates; Chalcones; Curcumin; Female; Leukemia, Experimental; Lymphoma; Mammary Neoplasms, Experimental; Mice

Anticancer activity of the rhizomes of turmeric was evaluated in vitro using tissue culture methods and in vivo in mice using Dalton's lymphoma cells grown as ascites form. Turmeric extract inhibited the cell growth in Chinese Hamster Ovary (CHO) cells at a concentration of 0.4 mg/ml and was cytotoxic to lymphocytes and Dalton's lymphoma cells at the same concentration. Cytotoxic effect was found within 30 min at room temperature (30 degrees C). The active constituent was found to be 'curcumin' which showed cytotoxicity to lymphocytes and Dalton's lymphoma cells at a concentration of 4 micrograms/ml. Initial experiments indicated that turmeric extract and curcumin reduced the development of animal tumours.

Topics: Animals; Antineoplastic Agents; Catechols; Cell Division; Cell Line; Cricetinae; Cricetulus; Curcumin; Female; Lymphocytes; Lymphoma; Mice; Ovary; Plant Extracts; Plants, Medicinal; Temperature; Time Factors