Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

In this study, we examined the antitumor effects of Puerarin (PEU) on androgen-independent (DU145 and PC-3) and androgen-dependent (LNCaP) prostate cancer cells, and explored its potential mechanisms. Supplement with PEU (2.5 mu M, 5 mu M, and 10 mu M) exhibited a marked inhibitory effect against the growth of DU145 and PC-3 cells, especially beyond 24 h, whereas there is only slight growth inhibitory effect on LNCaP cells at the high concentration of 10 mu M at 72 h. This loss of cell viability in DU145 and PC-3 cells by PEU was mediated by the induction of apoptosis via up-regulation of Bax and cleaved-caspase-3, but downregulation of Bcl-2. Moreover, more intracellular ROS and LDH production were observed in DU145 and PC-3 cells upon PEU treatment. Meanwhile, the amount of pro-inflammatory cytokines (IL-1 beta and IL-6) was increased, but the content of anti-inflammatory cytokines IL-10 was attenuated. Additionally, PEU pretreatment resulted in an increase of Keap1 protein expression, and a decline of Nrf2, HO-1 and NQO1 protein expression in DU145 and PC3 cells. The present findings indicated that PEU exerted its antitumor activities toward androgen-independent prostate cancer cells via inactivation of Keap1/NrF2/ARE signaling pathway. [GRAPHICS] .