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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the past several years we have been evaluating natural products as potential cancer chemopreventive agents in a short term in vitro assay involving Epstein--Barr virus early antigen (EBV-EA) activation in Raji cells promoted by phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Because of the current interest in the use of herbal remedies, we considered examining them for their cancer chemopreventive activities, using their extracts with a view to uncovering such benefits (if any) these remedies might possess. Thirty-six extracts of 32 herbs belonging to 27 families in use as herbal remedies including those of gingko, black cohosh, echinacea, kava-kava, saw palmetto, turmeric, angelica, wild yam, cat's claw, passion flower, muira puama, feverfew, blueberry, chasteberry, licorice, nettle, golden seal, pygeum, ginger, valerian and hops were prepared and evaluated. Turmeric at a concentration of 10 microg x ml (-1)exhibited the most potent anti-EBV-EA activity, which is ten times more than passionflower, that is next in the order of activity. At the concentration level of 100 microg ml (-1), several of the herbal remedies tested inhibited the EBV-EA in Raji cells exposed to the tumor promoter TPA (32 pM) by more than 90%. We also report for the first time the activities of 16 new medicinal plants as potential cancer chemopreventive agents. Since inhibitors of EBV-EA promoted by TPA in vitro have been shown to be effective anti-tumor promoting agents in laboratory animal models, our results indicate new and potential applications of these herbal remedies as cancer chemopreventive agents since they are already in clinical use in the human population.
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PMID:Inhibitory effect of herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein-Barr virus early antigen activation. 1188 18

Curcumin, the major component of the spice turmeric, is used as a coloring and flavoring additive in many foods and has attracted interest because of its anti-inflammatory and chemopreventive activities. However, this agent also inhibits the generation of reactive oxygen species (ROS) and the c-Jun NH(2)-terminal kinase (JNK) pathway, and because many chemotherapeutic drugs generate ROS and activate JNK in the course of inducing apoptosis, we considered the possibility that curcumin might antagonize their antitumor efficacy. Studies in tissue culture revealed that curcumin inhibited camptothecin-, mechlorethamine-, and doxorubicin-induced apoptosis of MCF-7, MDA-MB-231, and BT-474 human breast cancer cells by up to 70%. Inhibition of programmed cell death was time and concentration dependent, but occurred after relatively brief 3-h exposures, or at curcumin concentrations of 1 microM that have been documented in Phase I chemoprevention trials. Under these conditions, curcumin exhibited antioxidant properties and inhibited both JNK activation and mitochondrial release of cytochrome c in a concentration-dependent manner. Using an in vivo model of human breast cancer, dietary supplementation with curcumin was found to significantly inhibit cyclophosphamide-induced tumor regression. Such dietary supplementation was accompanied by a decrease in the activation of apoptosis by cyclophosphamide, as well as decreased JNK activation. These findings support the hypothesis that dietary curcumin can inhibit chemotherapy-induced apoptosis through inhibition of ROS generation and blockade of JNK function, and suggest that additional studies are needed to determine whether breast cancer patients undergoing chemotherapy should avoid curcumin supplementation, and possibly even limit their exposure to curcumin-containing foods.
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PMID:Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. 1294 49

Tea is one of the most popular beverages consumed in the world. Curcumin, the major yellow pigment in turmeric, is used widely as a spice and food-coloring agent. In this study, we studied the effects of tea and curcumin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. DMBA solution (0.5% in mineral oil, 0.1 ml) was applied topically to the left cheek pouch of male Syrian golden hamsters 3 times/week for 6 weeks. Two days after the last treatment of DMBA, the animals received green tea (6 mg tea solids/ml) as drinking fluid, or 10 mmol curcumin applied topically 3 times/week, or the combination of green tea and curcumin treatment, or no treatment for 18 weeks. The combination of tea and curcumin significantly decreased the oral visible tumor incidence from 92.3% (24/26) to 69.2% (18/26) and the squamous cell carcinoma (SCC) incidence from 76.9% (20/26) to 42.3% (11/26). The combination of tea and curcumin also decreased the number of visible tumors and the tumor volume by 52.4 and 69.8%, as well as the numbers of SCC, dysplasic lesions and papillomas by 62.0, 37.5 and 48.7%, respectively. Green tea or curcumin treatment decreased the number of visible tumors by 35.1 or 39.6%, the tumor volume by 41.6 or 61.3% and the number of SCC by 53.3 or 51.3%, respectively. Green tea also decreased the number of dysplasic lesions. Curcumin also significantly decreased the SCC incidence. Tea and curcumin, singly or in combination, decreased the proliferation index in hyperplasia, dysplasia and papillomas. Only the combination treatment decreased the proliferation index in SCC. Tea alone and in combination with curcumin significantly increased the apoptotic index in dysplasia and SCC. Curcumin, alone and in combination with tea, significantly inhibited the angiogenesis in papilloma and SCC. The results suggested that green tea and curcumin had inhibitory effects against oral carcinogenesis at the post-initiation stage and such inhibition may be related to the suppression of cell proliferation, induction of apoptosis and inhibition of angiogenesis.
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PMID:Inhibition of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters by tea and curcumin. 1215 48

Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in the tumor cells of a patient, resulting from enhanced drug efflux. It is often related to the overexpression of P-glycoprotein (Pgp) on the surface of tumor cells, thereby reducing drug cytotoxicity. In this study, curcumin was tested for its potential ability to modulate the expression and function of Pgp in the multidrug-resistant human cervical carcinoma cell line KB-V1. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) showed that treatment with 1, 5, and 10 microM curcumin for up to 72hr was able to significantly lower Pgp expression in KB-V1 cells. Curcumin (1-10 microM) decreased Pgp expression in a concentration-dependent manner and was also found to have the same effect on MDR1 mRNA levels. The effect of curcumin on Pgp function was demonstrated by rhodamine 123 (Rh123) accumulation and efflux in Pgp-expressing KB-V1 cells. Curcumin increased Rh123 accumulation in a concentration-dependent manner (1-55 microM) and inhibited the efflux of Rh123 from these cells, but did not affect the efflux of Rh123 from the wild-type drug-sensitive KB-3-1 cells. Treatment of drug-resistant KB-V1 cells with curcumin increased their sensitivity to vinblastine, which was consistent with an increased intracellular accumulation of Rh123. In addition, curcumin inhibited verapamil-stimulated ATPase activity and the photoaffinity labeling of Pgp with the prazosin analog [125I]iodoarylazidoprazosin in a concentration-dependent manner, demonstrating that curcumin interacts directly with the transporter. Thus, curcumin seems to be able to modulate the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells. In summary, this study describes the duel modulation of MDR1 expression and Pgp function by the phytochemical curcumin, which may be an attractive new agent for the chemosensitization of cancer cells.
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PMID:Modulation of P-glycoprotein expression and function by curcumin in multidrug-resistant human KB cells. 1216 76

Colorectal cancer is one of the leading causes of cancer deaths in the Western world. More than 56,000 newly diagnosed colorectal cancer patients die each year in the United States. Available therapies are either not effective or have unwanted side effects. Epidemiological data suggest that dietary manipulations play an important role in the prevention of many human cancers. Curcumin the yellow pigment in turmeric has been widely used for centuries in the Asian countries without any toxic effects. Epidemiological data also suggest that curcumin may be responsible for the lower rate of colorectal cancer in these countries. Curcumin is a naturally occurring powerful anti-inflammatory medicine. The anticancer properties of curcumin have been shown in cultured cells and animal studies. Curcumin inhibits lipooxygenase activity and is a specific inhibitor of cyclooxygenase-2 expression. Curcumin inhibits the initiation of carcinogenesis by inhibiting the cytochrome P-450 enzyme activity and increasing the levels of glutathione-S-transferase. Curcumin inhibits the promotion/progression stages of carcinogenesis. The anti-tumor effect of curcumin has been attributed in part to the arrest of cancer cells in S, G2/M cell cycle phase and induction of apoptosis. Curcumin inhibits the growth of DNA mismatch repair defective colon cancer cells. Therefore, curcumin may have value as a safe chemotherapeutic agent for the treatment of tumors exhibiting DNA mismatch repair deficient and microsatellite instable phenotype. Curcumin should be considered as a safe, non-toxic and easy to use chemotherapeutic agent for colorectal cancers arise in the setting of chromosomal instability as well as microsatellite instability.
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PMID:Chemotherapeutic potential of curcumin for colorectal cancer. 1217 41

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.
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PMID:Molecular mechanisms of anti-angiogenic effect of curcumin. 1235 44

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.
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PMID:Curcumin's effects on sialic acid level and sialidase activity in Ehrlich ascites tumor bearing mice. 1243 97

We have recently reported that osteopontin (OPN) stimulates tumor growth and activation of promatrix metalloproteinase-2 (pro-MMP-2) through nuclear factor kappa B (NF kappa B)-mediated induction of membrane type 1 matrix metalloproteinase (MT1-MMP) in murine melanoma cells (Philip, S., Bulbule, A., and Kundu, G. C. (2001) J. Biol. Chem. 276, 44926-44935). However, the molecular mechanism by which OPN activates NF kappa B and regulates pro-MMP-2 activation in murine melanoma (B16F10) cells is not well defined. We also investigated the mechanism of action of curcumin (diferulolylmethane) on OPN-induced NF kappa B-mediated activation of pro-MMP-2 in B16F10 cells. Here we report that OPN induces phosphorylation and degradation of the inhibitor of nuclear factor kappa B (I kappa B alpha) by inducing the activity of I kappa B kinase (IKK) in these cells. OPN also induces the nuclear accumulation of NF kappa B p65, NF kappa B-DNA binding, and transactivation. However, curcumin a known anti-inflammatory and anticarcinogenic agent suppressed OPN-induced I kappa B alpha phosphorylation and degradation by inhibiting the IKK activity. Moreover, our data revealed that curcumin inhibited the OPN-induced translocation of p65, NF kappa B-DNA binding, and NF kappa B transcriptional activity. The OPN-induced pro-MMP-2 activation and MT1-MMP expression were also drastically reduced by curcumin. Curcumin also inhibited OPN-induced cell proliferation, cell migration, extracellular matrix invasion, and synergistically induced apoptotic morphology with OPN in these cells. Most importantly, curcumin suppressed the OPN-induced tumor growth in nude mice, and the levels of pro-MMP-2 expression and activation in OPN-induced tumor were inhibited by curcumin. To our knowledge, this is the first report that OPN induces NF kappa B activity through phosphorylation and degradation of I kappa B alpha by activating IKK that ultimately triggers the activation of pro-MMP-2 and further demonstrates that curcumin potently suppresses OPN-induced cell migration, tumor growth, and NF kappa B-mediated pro-MMP-2 activation by blocking the IKK/I kappa B alpha signaling pathways.
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PMID:Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha /IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. 1247 70

The role of natural food products in prevention of prostate cancer has been confirmed in recent epidemiological studies; however, the mechanism of chemoprevention by the dietary constituents largely remains unknown. Curcumin, the yellow pigment and active component of turmeric (Curcuma longa), exhibits chemopreventive and growth inhibitory activity against several tumor cell lines. The androgen-sensitive human prostate cancer cell line LNCaP is only slightly susceptible to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family of cell death-inducing ligands. In this study, we investigated whether curcumin and TRAIL cooperatively interact to promote death of LNCaP cells. At low concentrations (10 micro M curcumin and 20 ng/ml TRAIL), neither of the two agents alone produced significant cytotoxicity (curcumin, <10%; TRAIL, approximately 15%) in LNCaP cells, as measured by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium dye reduction assay. On the other hand, cell death was markedly enhanced (2-3-fold) if tumor cells were treated with curcumin and TRAIL together. The combined curcumin and TRAIL treatment increased the number of hypodiploid cells and induced DNA fragmentation in LNCaP cells. The combined treatment induced cleavage of procaspase-3, procaspase-8, and procaspase-9, truncation of Bid, and release of cytochrome c from the mitochondria, indicating that both the extrinsic (receptor-mediated) and intrinsic (chemical-induced) pathways of apoptosis are triggered in prostate cancer cells treated with a combination of curcumin and TRAIL. These results define a potential use of curcumin to sensitize prostate cancer cells for TRAIL-mediated immunotherapy.
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PMID:Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells. 1253 77

0.5% DMBA solution (in mineral oil) was applied topically to the left cheek pouch of male Syrian golden hamsters 3 times per week for 6 weeks. After the last treatment of DMBA, the animals received 0.6% green tea powder as drinking fluid, or 10 mumol curcumin applied topically 3 times per week, or the combination of green tea and curcumin treatment, or no treatment for 18 weeks. The combination of tea and curcumin significantly decreased the oral visible tumor incidence and the squamous cell carcinoma (SCC) incidence. The combination of tea and curcumin also decreased the number of visible tumors and the tumor volume as well as the numbers of SCC, dysplasic lesions, and papillomas respectively. Green tea or curcumin treatment decreased the number of visible tumor, the tumor volume and the number of SCC respectively. Green tea also decreased the number of dysplasic lesions. Curcumin also significantly decreased the SCC incidence. Tea and curcumin, singly or in combination decreased bromodeoxyuridine (BrdU)-labeling index in hyperplasia, dysplasia, and papillomas. Tea alone and in combination with curcumin significantly increased the apoptotic index in dysplasia and SCC. Curcumin alone and in combination with tea inhibited the angiogenesis in papilloma and SCC. The results suggested that green tea and curcumin had inhibitory effects against oral carcinogenesis at the post-initiation stage and such inhibition may be related to the suppression of cell proliferation, induction of apoptosis, and inhibition of angiogenesis.
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PMID:[Chemopreventive effect of tea and curcumin on DMBA-induced oral carcinogenesis in hamsters]. 1257 55


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