Regulation of p53, BCL-2 and Caspase Dependent Signaling Pathway in Curcuma Extract-Induced Apoptosis of HepG2 Hepatoma Cells


Azimahtol Hawariah Lope Pihie


Traditional & Complementary Medicine Exhibition 2007 (TCME 2007), Putra World Trade Centre (PWTC), Kuala Lumpur, Malaysia




Data not available


This study investigated the antiproliferative effect and the mechanism of action ofCurcumaextract on human hepatoma cells, HepG2 and the mode of cell death. An antiproliferative assay using methylene blue staining revealed thatCurcumaextract inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 ± 0.053 μg/ml. The antiproliferative activity of Curcuma extract was due to apoptosis induced in the HepG2 cells and not necrosis, which was confirmed by the Tdt-mediated dUTP nick end labeling (TUNEL) assay. TheCurcumaextract-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage, and elongated lamellipodia. The apoptosis mediated byCurcumaextract in the HepG2 cells was associated with the activation of tumor suppressor p53 and down-regulation of antiapoptotic Bcl-2 protein expression, but not Bax. The levels of Bcl-2 protein expression decreased 24-hrs after treatment withCurcumaextract, and remained lower than controls throughout the experiment resulting in a shift in the Bax to Bcl-2 ratio thus favouring apoptosis. The processing of the initiator procaspase-9 was detected. Caspase-3 was also found to be activated, but not caspase-7.Curcumaextract exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.