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

Prateek Jain, Nitesh Kumar, Venkata Rao Josyula, Hitesh Vitthal Jagani, N. Udupa, C. Mallikarjuna Rao, Palanimuthu Vasanth Raj

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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 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.

Original languageEnglish
Pages (from-to)353-365
Number of pages13
JournalEuropean Journal of Pharmaceutical Sciences
Volume50
Issue number3-4
DOIs
Publication statusPublished - 2013

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Catechin
Caspases
Hep G2 Cells
Liposomes
Biological Availability
Cell Cycle
Body Weight
Apoptosis
Neoplasms
Caspase 9
Propidium
Fluorescein-5-isothiocyanate
G2 Phase
Annexin A5
DNA Fragmentation
Cytochromes c
In Vitro Techniques
Caspase 3
Cell Division
Antineoplastic Agents

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

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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 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.",
author = "Prateek Jain and Nitesh Kumar and Josyula, {Venkata Rao} and Jagani, {Hitesh Vitthal} and N. Udupa and {Mallikarjuna Rao}, C. and {Vasanth Raj}, Palanimuthu",
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AU - Jain, Prateek

AU - Kumar, Nitesh

AU - Josyula, Venkata Rao

AU - Jagani, Hitesh Vitthal

AU - Udupa, N.

AU - Mallikarjuna Rao, C.

AU - Vasanth Raj, Palanimuthu

PY - 2013

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N2 - 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 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.

AB - 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 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.

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