Xanthorrhizol induces apoptotic cell death through molecular cross talks between mitochondria-dependent and death receptor-mediated signaling in human promyelocytic leukemia cells

Abstract

Xanthorrhizol, isolated from Curcuma xanthorrhiza, has been shown to induce cell cycle arrest and apoptotic cell death by mainly mitochondrial-dependent signaling pathway in several human cancer cells. We investigated whether xanthorrhizol could apoptosis in HL-60 human promyelocytic leukemia cells. Xanthorrhizol treatment inhibited cell viability and induced apoptotic cell death. The levels of procaspase-3, -8 and -9 were reduced and the cleavage of full length PARP was clearly observed in xanthorrhizol-treated cells. Xanthorrhizol treatment did not affect Bcl-2 protein level but increased Bax protein level, resulting in the diminished Bcl-2/Bax ratio. The levels of cleaved Bid, Fas death receptor and p53, not FasL, were also increased by xanthorrhizol treatment. In conclusion, molecular cross talks between the intrinsic and extrinsic apoptotic pathway via Bid may play an important role for induction of apoptosis in xanthorrhizol-treated HL-60 cells. Therefore, xanthorrhizol has the chemorpeventive and anti-cancer potential against human promyelocytic leukemia cells