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Evaluation of Cisplatin in Combination with β‐Elemene as a Regimen for Prostate Cancer Chemotherapy
Author(s) -
Li Qingdi Quentin,
Wang Gangduo,
Reed Eddie,
Huang Lan,
Cuff Christopher F.
Publication year - 2010
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2010.00592.x
Subject(s) - cisplatin , du145 , prostate cancer , cancer research , apoptosis , elemene , chemosensitizer , lncap , medicine , cancer , prostate , pharmacology , chemotherapy , oncology , cytotoxicity , biology , in vitro , biochemistry
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.