Involvement of p53-mediated mitochondrial stress in the apoptosis induced by flavonoids purified from Rhus verniciflua stokes in human osteosarcoma cells

Dietary flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine and has long been used as a food additive and an antitumor agent in Korea. Previous study demonstrated that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), exhibited growth inhibition and induced apoptosis in human osteosarcoma (HOS) cells. This study evaluated if p53-mediated pathway is associated with the RCMF-induced apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis of the cells, as expected, and transparently increased p53 expression in the cells. However, the RCMF-induced cytotoxicity was suppressed by transfecting the cells with antisense p53 oligonucleotide, which also inhibited the decrease of Bcl-2 and the increase of Bax in mitochondria, and the release of cytochrome c into cytosol. This finding suggests that p53-mediated mitochondrial stress is required for RCMF-induced apoptosis in HOS cells.