title: 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.
authors.affiliation: Department of Microbiology, Immunology and Cell Biology, School of Medicine, West Virginia University Health Sciences Center, Morgantown, WV, USA. liquenti@niaid.nih.gov
authors.forename: Qingdi Quentin
authors.initials: QQ
authors.lastname: Li
authors.forename: Gangduo
authors.initials: G
authors.lastname: Wang
authors.forename: Eddie
authors.initials: E
authors.lastname: Reed
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Cuff
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D012717:Sesquiterpenes; C445979:beta-elemene; D020169:Caspases; D002945:Cisplatin