title: 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.
abstract: 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 μg mL(-1) depending on the length of exposure. It induced apoptosis and inhibited G₂/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 200mg/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.
authors: Cell and Molecular Biology Lab, Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors: Prateek
authors: P
authors: Jain
authors: Nitesh
authors: N
authors: Kumar
authors: Venkata Rao
authors: VR
authors: Josyula
authors: Hitesh Vitthal
authors: HV
authors: Jagani
authors: N
authors: N
authors: Udupa
authors: C
authors: C
authors: Mallikarjuna Rao
authors: Palanimuthu
authors: P
authors: Vasanth Raj
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008081:Liposomes; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D008081:Liposomes; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D002392:Catechin; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9
keywords: Catechin; Cell cycle and Ehrlich ascites carcinoma; Gene expression; HepG2 cells; Liposomes