BERBERINE CHLORIDE INDUCED APOPTOSIS IN HEPG2 CANCER CELL LINE VIA PPAR GAMMA ACTIVATION AND COX2 INHIBITION BY REGULATING PROSTAGLANDIN E2 (PGE2) SIGNALLING PATHWAY

Berberine hydrochloride is an isoquinoline alkaloid isolated in the form of Berberine hydrochloride from the roots and stems of Berberis vulgaris, B. aristata, Coptidis rhizoma and other plant species. Berberine is well known for its antiproliferative and anti inflammatory activity since long time. The present study is carried out to study mechanism of inducing apoptosis by berberine hydrochloride on HEPG2 liver cancer cell line. MTT assay used to study cytotoxicity against HEPG2 cells and COX2, PGE2 and western blot were used to study its apoptotic pathway. PGE2 has been implicated in COX-2-mediated effects; we determined the levels of PGE2 in the berberine-treated cells. Our results revealed that treatment with berberine hydrochloride for 24 h resulted in significant inhibition of PGE2 production in a dose-dependent manner 21-75%, P, 0.01-0.001, suggesting that berberine induced reduction in PGE2 production is associated with an inhibitory effect of the berberine on COX-2 in these cells. Berberine has shown PPAR Gamma activation and COX2 inhibition via PGE2 regulation and caused apoptosis by down regulating anti-apoptotic protein bcl-2 and upregulating bax and bak proteins. From the studies it is concluded that berberine hydrochloride can be a potential chemotherapeutic agent to treat Hepatocellular carcinoma.