Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 50, Issue 3-4, Pages 353-365Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2013.08.005
Keywords
HepG2 cells; Catechin; Liposomes; Gene expression; Cell cycle and Ehrlich ascites carcinoma
Categories
Funding
- DST-FIST (Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions)
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Catechin is a known hepatoprotective and anticancer agent but has limited bioavailability. Its apoptotic signaling pathway in human hepatocellular carcinoma is vaguely explored. Thus, this study was designed to explore cytotoxicity by MTT assay, induction of apoptosis via DNA fragmentation, nuclear staining, bivariate flow cytometric analysis using annexin V-FITC and propidium iodide, cell cycle analysis and apoptotic markers by RT-PCR and western blotting in HepG2 cells. To increase the bioavailability and selectivity to cancer cells, various liposomes of catechin viz., conventional, charged and PEGylated forms were prepared by film hydration method and evaluated for cytotoxicity in vitro in HepG2 cells and in in vivo in EAC-induced liquid tumor model. Catechin and catechin liposomes inhibited the growth of HepG2 cell lines at concentrations 100-200 mu g mL(-1) depending on the length of exposure. It induced apoptosis and inhibited G(2)/M phase in cell cycle analysis. Catechin downregulated Bcl-2, initiated the release of cytochrome c into the cytosol and upregulated Bax, caspase-3,-9 and p53 in the HepG2 cells. Catechin and its liposomal formulation, at a dose of 200 mg/kg body weight was found to be significantly (p < 0.05) effective in inhibiting percentage increase in body weight and enhancing the mean survival time. Deviated hematological parameters, antioxidant parameters (superoxide dismutase, catalase and lipid peroxidation) and LFT in tumor bearing mice were found to be significantly (p < 0.05) restored towards normal after treatment with catechin and its liposomes. (C) 2013 Elsevier B.V. All rights reserved.
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