Molecular Cancer Therapeutics 2014-06-01

Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells.

Yuzhe Tang, Ruibao Chen, Yan Huang, Guodong Li, Yiling Huang, Jiepeng Chen, Lili Duan, Bao-Ting Zhu, J Brantley Thrasher, Xu Zhang, Benyi Li

Index: Mol. Cancer Ther. 13(6) , 1526-36, (2014)

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Abstract

Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anticancer effect of a recently isolated natural compound, Alternol, in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived nonmalignant cells. As assessed by trypan blue exclusion assay, significant cell death was observed in all prostate cancer cell lines except DU145 but not in nonmalignant (RWPE-1 and BPH1) cells. Further analyses revealed that Alternol-induced cell death was an apoptotic response in a dose- and time-dependent manner, as evidenced by the appearance of apoptosis hallmarks such as caspase-3 processing and PARP cleavage. Interestingly, Alternol-induced cell death was completely abolished by reactive oxygen species scavengers N-acetylcysteine and dihydrolipoic acid. We also demonstrated that the proapoptotic Bax protein was activated after Alternol treatment and was critical for Alternol-induced apoptosis. Animal xenograft experiments in nude mice showed that Alternol treatment largely suppressed tumor growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data suggest that Alternol might serve as a novel anticancer agent for patients with late-stage prostate cancer.©2014 American Association for Cancer Research.