Evaluation of cisplatin in combination with β-elemene as a regimen for prostate cancer chemotherapy

Abstract

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumours. Nevertheless, it is not the first-line drug for prostate cancer chemotherapy, because prostate tumour cells exhibit intrinsic and acquired resistance to cisplatin. We have previously demonstrated that β-elemene, a novel plant-derived anti-neoplastic with low toxicity, inhibits lung and ovarian carcinoma cell growth in vitro. In the present study, we explored the therapeutically chemosensitizing effect of β-elemene on cisplatin anti-tumour efficacy in androgen-independent prostate cancer cells as well as the underlying mechanism. β-Elemene significantly increased cisplatin cytotoxicity in the androgen-independent prostate carcinoma cell lines DU145 and PC-3. In addition, β-elemene markedly promoted cisplatin-induced apoptotic cell death in both cell lines, as determined by three different apoptosis assays. β-Elemene augmented the cisplatin-induced activation of caspase-3/7/10 and caspase-9, cleavage of caspase-3 and -9, suppression of Bcl-2 and Bcl-X(L) expression, and release of cytochrome c from mitochondria in these cells. Thus, β-elemene enhancement of cisplatin-induced apoptosis via mitochondrial activation of the caspase-mediated apoptotic pathway may account for the augmented anti-cancer potency of cisplatin in prostate cancer. Cisplatin combined with β-elemene as a chemosensitizer or adjuvant warrants further study and may be potentially useful as a first-line treatment of androgen-independent prostate carcinomas.