Pinus massoniana bark extract selectively induces apoptosis in human hepatoma cells, possibly through caspase-dependent pathways

Abstract

Pinus massoniana bark extract (PMBE) is a mixture of flavonoids, whose antioxidant and apoptosis-inducing properties have been confirmed in vitro. In this study, the apoptotic effect and mechanism of PMBE in HepG2 human hepatoma cells were evaluated. PMBE exerted dose- and time-dependent cell growth inhibition on HepG2 cells, and selectively induced apoptosis without impact on normal liver L-02 cells. Apoptosis induced by PMBE in HepG2 cells was also confirmed by annexin-V/PI staining, transmission electron microscopy and sub-G1 phase accumulation. Moreover, PMBE also slightly blocked the cell cycle in the G2/M and S phases in HepG2 cells. The investigation of the mechanism by which PMBE induced apoptosis in HepG2 cells indicated that activation of extrinsic and intrinsic caspase, inhibition of NF-κB activation and decrease of the antiapoptotic protein Bcl-2 and the intact Bid protein were involved. Furthermore, the anti-tumor activity of PBME was demonstrated in vivo by a 42.88-69.94% reduction rate of tumor weight in H22 tumor-implanted mice. Taken together, these data indicate that PMBE selectively induces apoptosis in HepG2 cells through caspase-dependent pathways, and inhibits tumor growth in vivo, making it a potential candidate for anticancer therapeutics.