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Dietary supplementation of silymarin is associated with decreased cell proliferation, increased apoptosis, and activation of detoxification system in hepatocellular carcinoma.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2013 May; Vol. 377 (1-2), pp. 163-76. Date of Electronic Publication: 2013 Feb 09. - Publication Year :
- 2013
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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.
- Subjects :
- Animals
Carcinoma, Hepatocellular metabolism
Carcinoma, Hepatocellular pathology
Caspase 3 metabolism
Cells, Cultured
Cyclin D1 metabolism
Dietary Supplements
Drug Screening Assays, Antitumor
Glycoproteins metabolism
Hexosamines metabolism
Hexoses metabolism
Liver drug effects
Liver metabolism
Liver Neoplasms, Experimental metabolism
Liver Neoplasms, Experimental pathology
Male
Membrane Potential, Mitochondrial drug effects
Metabolic Detoxication, Phase II
Microtubule-Associated Proteins metabolism
Proliferating Cell Nuclear Antigen metabolism
Rats
Rats, Wistar
Sialic Acids metabolism
Survivin
Tumor Suppressor Protein p53 metabolism
beta Catenin metabolism
Antineoplastic Agents administration & dosage
Apoptosis drug effects
Carcinoma, Hepatocellular drug therapy
Cell Proliferation drug effects
Liver Neoplasms, Experimental drug therapy
Silymarin administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4919
- Volume :
- 377
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23397134
- Full Text :
- https://doi.org/10.1007/s11010-013-1582-1