curcumin and Carcinoma--Ehrlich-Tumor

Targeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH. The prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV-visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.. A significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).. In conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Ehrlich Tumor; Cell Proliferation; Curcumin; Doxorubicin; Drug Carriers; Drug Compounding; Drug Liberation; Endocytosis; HeLa Cells; Humans; Kinetics; Mice; Particle Size; Polyethylene Glycols; Spectroscopy, Fourier Transform Infrared; Tuftsin

In recent years, green synthesized silver nanoparticles have been increasingly investigated for their anti-cancer potential. In the present study, we aimed at the biosynthesis of silver nanoparticles (AgNPs) using a curcumin derivative, ST06. Although, the individual efficacies of silver nanoparticles or curcumin derivatives have been studied previously, the synergistic cytotoxic effects of curcumin derivative and silver nanoparticles in a single nanoparticulate formulation have not been studied earlier specifically on animal models. This makes this study novel compared to the earlier synthesized curcumin derivative or silver nanoparticles studies. The aim of the study was to synthesize ST06 coated silver nanoparticles (ST06-AgNPs) using ST06 as both reducing and coating agent.. The synthesized nanoparticles AgNPs and ST06-AgNPs were characterised for the particle size distribution, morphology, optical properties and surface charge by using UV-visible spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Elemental composition and structural properties were studied by energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction spectroscopy (XRD). The presence of ST06 as capping agent was demonstrated by Fourier transform infrared spectroscopy (FTIR).. The synthesized nanoparticles (ST06-AgNPs) were spherical and had a size distribution in the range of 50-100 nm. UV-Vis spectroscopy displayed a specific silver plasmon peak at 410 nm. The in vitro cytotoxicity effects of ST06 and ST06-AgNPs, as assessed by MTT assay, showed significant growth inhibition of human cervical cancer cell line (HeLa). In addition, studies carried out in EAC tumor-induced mouse model (Ehrlich Ascites carcinoma) using ST06-AgNPs, revealed that treatment of the animals with these nanoparticles resulted in a significant reduction in the tumor growth, compared to the control group animals.. In conclusion, green synthesized ST06-AgNPs exhibited superior anti-tumor efficacy than the free ST06 or AgNPs with no acute toxicity under both in vitro and in vivo conditions. The tumor suppression is associated with the intrinsic apoptotic pathway. Together, the results of this study suggest that ST06-AgNPs could be considered as a potential option for the treatment of solid tumors.

Topics: Animals; Apoptosis; Carcinoma, Ehrlich Tumor; Caspase 3; Caspase 9; Cell Death; Curcumin; Disease Models, Animal; Female; Green Chemistry Technology; HeLa Cells; Humans; Metal Nanoparticles; Mice; Particle Size; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-bcl-2; Silver; Spectrometry, X-Ray Emission; Spectroscopy, Fourier Transform Infrared; Tissue Distribution; Uterine Cervical Neoplasms; X-Ray Diffraction

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Screening Assays, Antitumor; Female; Humans; Male; Mice; Microtubules; Neoplasms

Curcumin is a natural pigment that generates singlet oxygen upon light excitation, hence it can be used as a photosensitizer in photodynamic therapy. The extremely low water solubility and poor systemic bioavailability make curcumin a challenging molecule to be used clinically. In this study, two nanocarrier systems for curcumin were prepared and characterized; nanoliposomes and polyvinyl pyrrolidone-capped gold nanoparticles. The dark and photocytotoxicity were investigated as a function of light fluence rate (100 and 200 mW/cm

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Curcumin; Drug Liberation; Hep G2 Cells; Humans; Liposomes; Male; Metal Nanoparticles; Mice; Nanoparticles; Particle Size; Photochemotherapy; Spectroscopy, Fourier Transform Infrared

Doxorubicin (DOX) has been extensively used to treat a wide range of cancers in free and nanotized form. Nanotization of DOX has alleviated its toxicity and efflux-mediated resistance. However, frequent upregulation of anti-apoptotic pathways, chemotherapy-enhanced inflammation, and epithelial-mesenchymal transition (EMT), present additional aspects of cellular DOX résistance. Nanoparticle-mediated combination therapy of DOX with additional anticancer agents is expected to offer greater therapeutic benefit by alleviating the overall drug résistance. We synthesized CD44-targeted DOX loaded nanoparticles (PSHA-DOXNPs) and evaluated their anticancer efficacy in combination with curcumin loaded selenium nanoparticles (Se-Cur NPs), previously developed by our group (Kumari et al., 2017). Combination of these nanoparticles (NPs) increased ROS level, decreased mitochondrial membrane potential, induced cell cycle arrest and apoptosis in HCT116 cells. This combination decreased the expressions of NFκB, Phospho-NFκB, EMT-metastasis-associated proteins (Snail, Vimentin, N-cadherin, CD44, MMP-2 and MMP-9), autophagy-associated proteins (Beclin-1 and LC-3BII), as well as anti-apoptotic protein Bcl-2, increased the expression of pro-apoptotic protein Bax, and increased cyt c release, which indicated decrease in inflammation, metastasis, and autophagy with increase in apoptosis. Moreover, the combination of NPs decreased tumor burden and increased survival of Ehrlich's ascites carcinoma (EAC)-bearing mice.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Autophagy; Carcinoma, Ehrlich Tumor; Cell Survival; Curcumin; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Resistance, Neoplasm; Drug Synergism; Female; HCT116 Cells; Humans; Hyaluronan Receptors; Mice; Nanoparticles; Selenium

The anticancer properties of selenium (Se) and curcumin nanoparticles in solo formulations as well as in combination with other therapeutic agents have been proved time and again. Exploiting this facet of the two, we clubbed their tumoricidal characteristics and designed curcumin loaded Se nanoparticles (Se-CurNPs) to achieve an enhanced therapeutic effect. We evaluated their therapeutic effects on different cancer cell lines and Ehrlich's ascites carcinoma mouse model. In vitro results showed that Se-CurNPs were most effective on colorectal carcinoma cells (HCT116) compared to the other cancer cell lines used and possessed pleiotropic anticancer effects. The therapeutic effect on HCT116 was primarily attributed to an elevated level of autophagy and apoptosis as evident from significant up-regulation of autophagy associated (LC3B-II) and pro-apoptotic (Bax) proteins, down-regulation of anti-apoptotic (Bcl-2) protein and Cytochrome c (cyt c) release from mitochondria along with reduced NFκB signaling and EMT based machineries marked by downregulation of inflammation (NFκB, phospho-NFκB) and epithelial-mesenchymal transition (CD44, N-cadherin) associated proteins. In vivo studies on Ehrlich's ascites carcinoma (EAC) mice model indicated that Se-CurNPs significantly reduced the tumor load and enhanced the mean survival time (days) of tumor-bearing EAC mice.

Topics: A549 Cells; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Curcumin; Dose-Response Relationship, Drug; Drug Carriers; HCT116 Cells; Humans; Male; MCF-7 Cells; Mice; Nanoparticles; Selenium; Treatment Outcome; Xenograft Model Antitumor Assays

Curcumin is a polyphenol compound that has antioxidant, anticancer, anti-inflammatory, anti-hyperlipidemic and antimicrobial effects. Nucleolar-organizing regions are the sites of the gene on chromosomes. The present study was aimed to show the antitumoral effect of curcumin via AgNOR protein synthesis in Ehrlich's ascitic carcinoma (EAC) bearing mice.. Twenty three mice with EAC were randomly divided into 3 groups as positive control (n = 7), group 2 (n = 8) and 3 (n = 8) treated intraperitoneally with curcumin (25 mg/kg) and (50 mg/kg), respectively. The animals were sacrificed on Day 16, the solid tumors were removed out. Then, total AgNOR area/nuclear area (TAA/NA) and the mean AgNOR number were estimated for each mice.. Statistically significant differences were determined among the whole groups for TAA/NA ratio (p = 0.000), conversely mean AgNOR number (p = 0.361). When comparingthe two groups; while no difference was determined between the control and curcumin (25 mg/kg) groups (p = 0.061), the significant differences were detected between the control and curcumin (50 mg/kg) groups (p = 0.000) and between curcumin (25 mg/kg) and curcumin (50 mg/kg) groups (p = 0.000) for TAA/NA ratio. However, there was no significant difference for the mean AgNOR number in double comparison of the groups.. The current study showed that curcumin had a crucial function against cancer development. Also, both AgNOR values might be used as biomarkers for detection of the most reliable therapeutic dose selection of cancer treatment (Tab. 3, Fig. 2, Ref. 27).

Topics: Animals; Antigens, Nuclear; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Curcumin; Female; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation

New curcumin analogues have been synthesized and their antioxidant activities were investigated by measuring their free radical scavenging capacities. The in vitro and in vivo antitumor activities of the synthesized compounds on Ehrlich ascites carcinoma (EAC) cell line were evaluated. 4-(4-Chlorophenyl)-2-(5-ethyl-7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c] pyridin-2-yl)thiazole 7h showed excellent antineoplastic activity in both in vitro and in vivo studies more than that of tested compounds and reference drug, cisplatin. Different molecular modeling studies were performed, where docking of compound 7h into telomerase active site suggested that it could exert its antitumor potential by telomerase inhibition.

Topics: Animals; Antineoplastic Agents; Antioxidants; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Cell Proliferation; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Humans; Mice; Models, Molecular; Molecular Structure; Neoplasms, Experimental; Structure-Activity Relationship

Curcuma caesia Roxb. (Zingiberaceae), commonly known as "Kala Haldi" in Bengali, has been traditionally used for the treatment of cancer, bruises, inflammation and as an aphrodisiac.. To evaluate the antitumor activity and antioxidant status of the methanol extract of Curcuma caesia (MECC) rhizomes on Ehrlich's ascites carcinoma (EAC)-treated mice.. In vitro cytotoxicity assay of MECC was evaluated by using Trypan blue method. Determination of in vivo antitumor activity was performed after 24 h of EAC cells (2 × 10(6) cells/mouse) inoculation; MECC (50 and 100 mg/kg i.p.) was administered daily for nine consecutive days. On day 10, half of the mice were sacrificed and the rest were kept alive for assessment of increase in lifespan. Antitumor effect of MECC was assessed by the study of tumor volume, tumor weight, viable and non-viable cell count, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes.. MECC showed direct cytotoxicity (IC50 90.70 ± 8.37 μg/mL) on EAC cell line. MECC exhibited significant (p < 0.01) decrease in tumor volume, tumor weight, viable cell count and percentage increased the lifespan (57.14 and 88.09%) of EAC-treated mice. Hematological profile, biochemical estimation, tissue antioxidant assay significantly (p < 0.01) reverted to normal level in MECC-treated mice.. MECC possesses potent antitumor activity that may be due to its direct cytotoxic effect or antioxidant properties. Further research is in progress to find out the active principle(s) of MECC for its antitumor activity.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Carcinoma, Ehrlich Tumor; Curcuma; India; Inhibitory Concentration 50; Kidney; Liver; Male; Medicine, Traditional; Mice; Plant Extracts; Rhizome

Curcumin has long been used as an antioxidative, antiinflammatory, and modulator of pathological angiogenesis, whereas naringenin is a well-known immunomodulator. In this report, we investigated the effect of curcumin and naringenin on the growth of Ehrlich ascites carcinoma tumor model. To achieve this, Swiss albino mice were implanted intraperitoneally with 1 × 10⁶ Ehrlich ascites carcinoma cells followed by the administration of oral doses of naringenin and curcumin either individually (50 mg/kg body weight) or in combination (20 mg/kg body weight each). A marked reduction has been seen in the total number of cells (80%) and accumulation of ascetic fluid (55%) when these drugs were administered together. These drugs proved to be an effective angio-inhibitory compound and confirmed by different in vivo assay systems, viz. peritoneal/skin angiogenesis and chorioallantoic membrane assay. Antiangiogenic and antiproliferative effect of these compounds alone or in combination was further corroborated with immunoblot results where we confirmed the downregulation of vascular endothelial growth factor, Hif1α, heat shock protein 90, and p-Akt. Furthermore, treatment with naringenin and curcumin alone or in combination substantially improved hepatocellular architecture and no noticeable neoplastic lesions or cellular alteration were reported. These outcomes put forward a plausible clinical application of these diet-derived compounds, as both angioinhibitory and antitumor in association with conventional therapy.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Carcinoma, Ehrlich Tumor; Cell Proliferation; Chick Embryo; Chorioallantoic Membrane; Curcumin; Female; Flavanones; Liver; Mice; Neoplasm Transplantation; Neovascularization, Pathologic; Peritoneum; Survival Analysis; Tissue Culture Techniques; Tumor Burden

The phytochemicals, resveratrol or curcumin, have been shown to possess many pharmacological activities including anti-inflammatory, anti-oxidant, anti-microbial and anti-cancer effects. However, the underlying mechanism for their anti-tumor activity is yet to be evaluated. The present study was carried out to investigate the anti-angiogenic effect of resveratrol or curcumin when used alone or in combination with carboplatin in Ehrlich ascites carcinoma (EAC)-bearing mice. Solid tumors were induced by intradermal injection of EAC cells. These tumors were used for the evaluation of microvessel density, plasma vascular endothelial growth factor (VEGF) and its intra-tumoral receptor type-2 (Flk-1). All parameters were determined as a time course on days 7, 14, and 21 post-inoculation. Individual treatments with resveratrol or curcumin and their combination with carboplatin produced a significant reduction in microvessel density. Plasma levels of VEGF were significantly reduced in groups treated with resveratrol or curcumin and their combination with carboplatin on day 7 post-inoculation. Treatment with resveratrol or curcumin reduced the percentage of Flk-1-rich tumors to reach 42.9% and 28.6%, respectively. Their co-administration with carboplatin has produced a further reduction in the percentage of Flk-1-rich tumors to reach 28.6% and 14.3%, respectively. Correlation studies showed strong association between plasma VEGF and microvessel density. In conclusion, resveratrol or curcumin inhibited angiogenesis as demonstrated by the reduction of microvessel density by these agents. Both proved to exert their anti-angiogenic effect by inhibition of VEGF and its receptor type-2. The results suggest the beneficial role of these phytochemicals as adjuvant to chemotherapy in the treatment of cancer.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Curcumin; Mice; Neoplasms, Experimental; Neovascularization, Pathologic; Resveratrol; Stilbenes; Time Factors; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

In the present study, four novel dienone cyclopropoxy curcumin analogs 1a-4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a-4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a-4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance.

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Carcinoma, Ehrlich Tumor; Curcumin; Drug Screening Assays, Antitumor; Mice; Molecular Structure

One of the most clinically relevant biological activities of curcumin is its anti-cancer property, implicating multiple intracellular pathways in the process. In the present report, we investigated the effect of curcumin on the activation of apoptotic and anti-angiogenic pathways in Ehrlich Ascites Tumor (EAT) cells. Treatment with curcumin in vivo resulted in inhibition of proliferation of EAT cells and ascites formation. Further, we demonstrate that the induction of apoptosis in EAT cells showed nuclear condensation, DNA fragmentation and translocation of caspase-activated DNase (CAD) to nucleus upon curcumin treatment. Curcumin-induced apoptosis is mediated through activation of caspase-3, which is specifically inhibited by the caspase-3 inhibitor, Ac-DEVD-CHO. On the other hand, the decreased secretion of ascites by EAT cells is corroborated by reduction in VEGF secretion upon curcumin treatment. Further, CD31 immunohistological staining of peritoneum sections in curcumin-treated mice suggests its efficacy in acting as anti-angiogenic compound in EAT cells by inhibiting proliferation of endothelial cells in mouse peritoneum. However, immunoflurescence studies of NF-kB revealed that the inhibition of nuclear translocation of NF-kB p65, a transcription factor required for VEGF gene expression, in curcumin-treated EAT cells. These results suggest a further possible clinical application of this diet-derived compound curcumin, as both proapoptotic and anti-angiogenic compound in association with conventional chemotherapeutic agents.

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Carcinoma, Ehrlich Tumor; Caspase 3; Caspases; Cell Nucleus; Cell Proliferation; Curcumin; Deoxyribonucleases; Endothelium, Vascular; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Mice; Neovascularization, Pathologic; NF-kappa B; Protein Transport; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

The true therapeutic benefit of the use of natural products, especially acceptable dietary components such as curcumin, which can spare the normal cells and boost host immunity, has opened new horizons in cancer prevention and treatment.. In our model system we used Ehrlich's ascites carcinoma cells grown in peritoneal carity of Swiss albino mice and curcumin was fed every alternative day.. Here, we report that curcumin administration to tumor-bearing mice decreased tumor cell number significantly in a dose-dependent manner. Furthermore, tumor-induced depletion of immune cell number of the host, as was evidenced from the decrease in bone marrow progenitor as well as thymic and splenic mononuclear cell numbers, was reintrated by curcumin. In fact, curcumin inhibited tumor-induced apoptosis of both thymocytes and splenocytes thereby restoring immune cell numbers to normal level in treated Ehrlich's ascites carcinoma-bearing mice. Moreover, curcumin was not toxic to the host; rather in tumor-bearing mice it inhibited hematopoietic toxicity, acted as a hepatoprotective agent and activated depressed anti-oxidant and detoxification systems.. The ability of curcumin to regress tumor as well as to protect the host from tumor-induced immunosuppression and toxicity strongly supports the candidacy of curcumin as a potential agent for the dietary therapy of cancer.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Carcinoma, Ehrlich Tumor; Curcumin; Immunity, Cellular; Immunosuppression Therapy; Mice; Monocytes; Spleen; Thymus Gland

Four synthetic curcuminoids, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione (curcumin1), 1,7-bis(piperonyl)-1,6-heptadiene-3, 5-dione (piperonyl curcumin), 1, 7-bis(2-hydroxy naphthyl)-1, 6-heptadiene-2, 5-dione (2-hydroxy naphthyl curcumin), 1,1-bis(phenyl)-1, 3, 8, 10- undecatetraene-5, 7-dione (cinnamyl curcumin) and their copper(II) complexes were investigated for their possible cytotoxic and antitumour activities. Copper chelates of synthetic curcuminoids showed enhanced antitumour activity. All the compounds were found to be cytotoxic to cultured L929 cells, concentration needed for 50% inhibition being around 10 microg/ml for curcuminoids and 1 microg/ml for their copper complexes. Copper complexes of curcuminoids with a hydroxy group on the ring such as 2-hydroxy naphthyl curcumin were found to be most active (1 microg/ml produced 60.45+/-2.1% cell death). Copper complex of cinnamyl curcumin which has an extended conjugation showed considerable activity in increasing the life span (ILS=78.6%) of ascites tumour bearing animals. Whereas complex of piperonyl curcumin was found to show least antitumour activity. Copper chelates of curcuminoids showed a significant reduction (p< .001) of solid tumour volume in mice.

Topics: Animals; Anticarcinogenic Agents; Carcinoma, Ehrlich Tumor; Cell Division; Cell Survival; Chelation Therapy; Copper; Curcumin; Female; Mice; Tumor Cells, Cultured

Modulation of pathological angiogenesis by curcumin (diferuloylmethane), the active principle of turmeric, seems to be an important possibility meriting mechanistic investigations. In this report, we have studied the effect of curcumin on the growth of Ehrlich ascites tumor cells and endothelial cells in vitro. Further, regulation of tumor angiogenesis by modulation of angiogenic ligands and their receptor gene expression in tumor and endothelial cells, respectively, by curcumin was investigated. Curcumin, when injected intraperitoneally (i.p) into mice, effectively decreased the formation of ascites fluid by 66% in EAT bearing mice in vivo. Reduction in the number of EAT cells and human umbelical vein endothelial cells (HUVECs) in vitro by curcumin, without being cytotoxic to these cells, is attributed to induction of apoptosis by curcumin, as is evident by an increase in cells with fractional DNA content seen in our results on FACS analysis. However, curcumin had no effect on the growth of NIH3T3 cells. Curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in two in vivo angiogenesis assay systems, viz. peritoneal angiogenesis and chorioallantoic membrane assay. The angioinhibitory effect of curcumin in vivo was corroborated by the results on down-regulation of the expression of proangiogenic genes, in EAT, NIH3T3, and endothelial cells by curcumin. Our results on Northern blot analysis clearly indicated a time-dependent (0-24h) inhibition by curcumin of VEGF, angiopoietin 1 and 2 gene expression in EAT cells, VEGF and angiopoietin 1 gene expression in NIH3T3 cells, and KDR gene expression in HUVECs. Further, decreased VEGF levels in conditioned media from cells treated with various doses of curcumin (1 microM-1mM) for various time periods (0-24h) confirm its angioinhibitory action at the level of gene expression. Because of its non-toxic nature, curcumin could be further developed to treat chronic diseases that are associated with extensive neovascularization.

Topics: 3T3 Cells; Angiogenesis Inhibitors; Animals; Carcinoma, Ehrlich Tumor; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Humans; Mice; Neovascularization, Pathologic; Tumor Cells, Cultured; Umbilical Veins

In this study, we determined curcumin's anticancer and chemopreventive effects in mice bearing Ehrlich ascites tumor by evaluation of cancer biomarkers, sialic acid level and sialidase activity. Both plasma sialic acid level and sialidase activity increased significantly in the mice group with Ehrlich ascites tumor. When the tumor groups fed with curcumin and fed with sesame oil were compared, sialic acid level and sialidase activity in ascites fluid significantly reduced in the group fed with curcumin in addition to the increases of plasma sialic acid level and sialidase activity. The tumor group fed with curcumin lived twice longer than the one fed with sesame oil. Curcumin as a phenolic compound decreased all these parameters in Ehrlich ascites tumors and lengthened survival by 88% in the mice with tumor. We concluded that curcumin has anticancer activity.

Topics: Animals; Antineoplastic Agents; Ascitic Fluid; Biomarkers; Carcinoma, Ehrlich Tumor; Curcumin; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neuraminidase; Sialic Acids; Tumor Cells, Cultured

Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is a potent antioxidant and anti-inflammatory agent. It has been recently demonstrated to possess discrete chemopreventive activities. However, the molecular mechanisms underlying such anticancer properties of curcumin still remain unrealized, although it has been postulated that induction of apoptosis in cancer cells might be a probable explanation. In the current study, curcumin was found to decrease the Ehrlich's ascites carcinoma (EAC) cell number by the induction of apoptosis in the tumor cells as evident from flow-cytometric analysis of cell cycle phase distribution of nuclear DNA and oligonucleosomal fragmentation. Probing further into the molecular signals leading to apoptosis of EAC cells, we observed that curcumin is causing tumor cell death by the up-regulation of the proto-oncoprotein Bax, release of cytochrome c from the mitochondria, and activation of caspase-3. The status of Bcl-2 remains unchanged in EAC, which would signify that curcumin is bypassing the Bcl-2 checkpoint and overriding its protective effect on apoptosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Ehrlich Tumor; Caspase 3; Caspases; Cell Count; Cell Cycle; Curcumin; Cytochrome c Group; Cytosol; DNA Fragmentation; DNA, Neoplasm; Flow Cytometry; Male; Mice; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

Matural curcuminoids, curcumin, I, II and III isolated from turmeric (Curcuma longa) were compared for their cytotoxic, tumour reducing and antioxidant activities. Curcumin III was found to be more active than the other two as a cytotoxic agent and in the inhibition of Ehrlich ascites tumour in mice (ILS 74.1%). These compounds were also checked for their antioxidant activity which possibly indicates their potential use as anti-promoters. The amount of curcuminoids (I, II and III) needed for 50% inhibition of lipid peroxidation was 20, 14 and 11 g/m. Concentrations needed for 50% inhibition of superoxides were 6.25, 4.25 and 1.9 micrograms/ml and those for hydroxyl radical were 2.3, 1.8 and 1.8 micrograms/ml, respectively. The ability of these compounds to suppress the superoxide production by macrophages activated with phorbol-12-myristate-13-acetate (PMA) indicated that all the three curcuminoids inhibited superoxide production and curcumin III produced maximum effect. These results indicate that curcumin III is the most active of the curcuminoids present in turmeric. Synthetic curcumin I and III had similar activity to natural curcumins.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Carcinoma, Ehrlich Tumor; Curcumin; Drug Screening Assays, Antitumor; Hydroxyl Radical; Lipid Peroxidation; Mice; Superoxides