title: β-elemene effectively suppresses the growth and survival of both platinum-sensitive and -resistant ovarian tumor cells.
abstract: The development of cisplatin drug resistance remains a chief concern in ovarian cancer chemotherapy. β-Elemene is a natural plant product with broad-spectrum antitumor activity towards many types of carcinomas. This study aimed to define the biological and therapeutic significance of β-elemene in chemoresistant ovarian cancer. In the present study, β-elemene significantly inhibited cell growth and proliferation of both the cisplatin-sensitive human ovarian cancer cell line A2780 and its cisplatin-resistant counterpart A2780/CP. β-Elemene also suppressed the growth of several other chemosensitive and chemoresistant ovarian cancer cell lines, including ES-2, MCAS, OVCAR-3, and SKOV-3, with the half maximal inhibitory concentration (IC(50)) values ranging from 54 to 78 μg/ml. In contrast, the IC(50) values of β-elemene for the human ovarian epithelial cell lines IOSE-386 and IOSE-397 were 110 and 114 μg/ml, respectively, which are almost two-fold those for the ovarian cancer cell lines. Cell cycle analysis demonstrated that β-elemene induced a persistent block of cell cycle progression at the G(2)/M phase in A2780 and A2780/CP cells. This was mediated by alterations in cyclin and cyclin-dependent kinase expression, including the down-regulation of CDC2, cyclin A, and cyclin B1, and the up-regulation of p21(WAF1/CIP1) and p53 proteins. Moreover, β-elemene triggered apoptosis and irreversible cell death in both sensitive and resistant ovarian cancer cells via the activation of caspase-3, -8 and 9; the loss of mitochondrial membrane potential (δΨm); the release of cytochrome c into the cytosol; and changes in the expression of BCL-2 family proteins. All of these molecular changes were associated with β-elemene-induced growth inhibition and cell death of ovarian cancer cells. Our results demonstrate that β-elemene has antitumor activity against both platinum-sensitive and resistant ovarian cancer cells, and thus has the potential for development as a chemotherapeutic agent for cisplatin-resistant ovarian cancer.
authors: Department of Microbiology, Immunology and Cell Biology, Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV, USA.
authors: Rebecca X
authors: RX
authors: Lee
authors: Qingdi Quentin
authors: QQ
authors: Li
authors: Eddie
authors: E
authors: Reed
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D010051:Ovarian Neoplasms / Q000473:pathology*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C445979:beta-elemene; D002945:Cisplatin