Isoalantolactone, a medicinal plant-derived natural compound, is known to induce apoptosis in various
cancer cell lines. However, its effect on apoptosis in
prostate cancer cells has not been addressed. Thus, we examined the effects of
isoalantolactone on
prostate cancer cells. It was found that
isoalantolactone inhibits growth of both
androgen-sensitive (LNCaP) as well as
androgen-independent (PC3 and DU-145)
prostate cancer cells in a dose-dependent manner. Furthermore, our results indicate that
isoalantolactone-induced apoptosis in
prostate cancer PC3 cells is associated with the generation of ROS and dissipation of mitochondrial membrane potential (Δψm). In addition,
isoalantolactone triggers apoptosis in
prostate cancer cells via up-regulation of Bax, down-regulation of Bcl-2,
survivin, and significant activation of
caspase-3.
Isoalantolactone-induced apoptosis is markedly abrogated when the cells were pretreated with
N-acetylcysteine (NAC), a specific ROS inhibitor, suggesting that the apoptosis-inducing effect of
isoalantolactone in
prostate cancer cells is mediated by
reactive oxygen species. These findings indicate that
isoalantolactone induces
reactive oxygen species-dependent apoptosis in
prostate cancer cells via a novel mechanism involving inhibition of
survivin and provide the rationale for further in vivo and preclinical investigation of
isoalantolactone against human
prostate cancer.