Xanthorrhizol is a
sesquiterpenoid compound extracted from the rhizome of Curcuma xanthorrhiza. This study investigated the antiproliferative effect and the mechanism of action of
xanthorrhizol on human
hepatoma cells, HepG2, and the mode of cell death. An antiproliferative assay using
methylene blue staining revealed that
xanthorrhizol inhibited the proliferation of the HepG2 cells with a 50% inhibition of cell growth (IC50) value of 4.17 +/- 0.053 microg/ml. The antiproliferative activity of
xanthorrhizol 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. The
xanthorrhizol-treated HepG2 cells showed typical apoptotic morphology such as DNA fragmentation, cell shrinkage and elongated lamellipodia. The apoptosis mediated by
xanthorrhizol 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-h
after treatment with
xanthorrhizol 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.
Xanthorrhizol exerts antiproliferative effects on HepG2 cells by inducing apoptosis via the mitochondrial pathway.