A study on the role of (+)-catechin in suppression of HepG2 proliferation via caspase dependent pathway and enhancement of its in vitro and in vivo cytotoxic potential through liposomal formulation

Jain, Prateek and Nitesh, Kumar and Josyula, Venkata Rao and Jagani, Vitthal Hitesh and Udupa, N and Rao, Mallikarjuna C and Palanimuthu, Vasanth Raj (2013) A study on the role of (+)-catechin in suppression of HepG2 proliferation via caspase dependent pathway and enhancement of its in vitro and in vivo cytotoxic potential through liposomal formulation. European Journal of Pharmaceutical Sciences. pp. 1-13.

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Abstract

Catechin is a known hepatoprotective and anticancer agent but has limited bioavailability. Its apoptotic 30 signaling pathway in human hepatocellular carcinoma is vaguely explored. Thus, this study was designed 31 to explore cytotoxicity by MTT assay, induction of apoptosis via DNA fragmentation, nuclear staining, 32 bivariate flow cytometric analysis using annexin V- FITC and propidium iodide, cell cycle analysis and 33 apoptotic markers by RT-PCR and western blotting in HepG2 cells. To increase the bioavailability and 34 selectivity to cancer cells, various liposomes of catechin viz., conventional, charged and PEGylated forms 35 were prepared by film hydration method and evaluated for cytotoxicity in vitro in HepG2 cells and in 36 in vivo in EAC-induced liquid tumor model. Catechin and catechin liposomes inhibited the growth of 37 HepG2 cell lines at concentrations 100–200 lg mL�1 depending on the length of exposure. It induced 38 apoptosis and inhibited G2/M phase in cell cycle analysis. Catechin downregulated Bcl-2, initiated the 39 release of cytochrome c into the cytosol and upregulated Bax, caspase-3,-9 and p53 in the HepG2 cells. 40 Catechin and its liposomal formulation, at a dose of 200 mg/kg body weight was found to be significantly 41 (p < 0.05) effective in inhibiting percentage increase in body weight and enhancing the mean survival 42 time. Deviated hematological parameters, antioxidant parameters (superoxide dismutase, catalase and 43 lipid peroxidation) and LFT in tumor bearing mice were found to be significantly (p < 0.05) restored 44 towards normal after treatment with catechin and its liposomes.

Item Type: Article
Uncontrolled Keywords: HepG2 cells; Catechin; Liposomes; Gene expression; Cell cycle and Ehrlich ascites carcinoma
Subjects: Pharmacy > MCOPS Manipal > Pharmaceutical Biotechnology
Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Manipal
Date Deposited: 28 Aug 2013 04:14
Last Modified: 28 Aug 2013 04:14
URI: http://eprints.manipal.edu/id/eprint/136944

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