title: Dietary supplementation of silymarin is associated with decreased cell proliferation, increased apoptosis, and activation of detoxification system in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world. HCC's limited treatment remedies and the poor prognosis emphasize the importance in developing an effective chemoprevention for this disease. Here, we investigated the molecular mechanisms involved in the chemoprevention of silymarin in N-nitrosodiethylamine (NDEA)-induced rat model of HCC. Liver of the rats treated with NDEA showed higher proliferation index and glycoconjugates. NDEA treatment also increased the level of anti-apoptotic proteins with simultaneous decrease in the level of pro-apoptotic proteins along with increased accumulation of Cytochrome c in mitochondria. The carcinogenic insult also increased microsomal phase I metabolizing enzymes with a simultaneous decrease in the Phase II detoxifying enzyme glutathione-S-transferase (GST). Whereas dietary silymarin administration along with NDEA treatment significantly decreased the proliferation and down regulated the expression of anti-apoptotic proteins with simultaneously increased expression of pro-apoptotic proteins along with the release of Cytochrome c to cytosol there by activating the intrinsic apoptotic pathway. Silymarin administration also decreased the level of glycoproteins and activated the phase II detoxifying enzyme GST. These results demonstrate that suppression of HCC by silymarin in vivo involves inhibition of proliferation, activation of apoptosis, and efficient detoxification.
authors: Department of Biochemistry, University of Madras, Guindy campus, Chennai, Tamil Nadu, India.
authors: Ramakrishnan
authors: R
authors: Gopalakrishnan
authors: Jagan
authors: J
authors: Sundaram
authors: Kamaraj
authors: K
authors: Sattu
authors: Anandakumar
authors: A
authors: Pandi
authors: Devaki
authors: D
authors: Thiruvengadam
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D019587:Dietary Supplements; D004354:Drug Screening Assays, Antitumor; D006023:Glycoproteins / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D050217:Metabolic Detoxication, Phase II; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism; D012838:Silymarin / Q000008:administration & dosage*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C516989:Birc5 protein, rat; C530106:Ccnd1 protein, rat; D006023:Glycoproteins; D006595:Hexosamines; D006601:Hexoses; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D012794:Sialic Acids; D012838:Silymarin; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D019938:Cyclin D1; C505410:Casp3 protein, rat; D053148:Caspase 3
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