| Title: | "Anti-proliferative effect of 23,24-dihydrocucurbitacin F on human prostate cancer cells through induction of actin aggregation and cofilin-actin rod formation" |
| Author(s): | Ren S; Ouyang DY; Saltis M; Xu LH; Zha QB; Cai JY; He XH; |
| Address: | "Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou, China" |
| Journal Title: | Cancer Chemother Pharmacol |
| DOI: | 10.1007/s00280-012-1921-z |
| ISSN/ISBN: | 1432-0843 (Electronic) 0344-5704 (Linking) |
| Abstract: | "PURPOSE: The cucurbitacins are a class of triterpenoid molecules that possess cytotoxic characteristics for plant defense against herbivore feeding. 23,24-dihydrocucurbitacin F (DHCF), a derivative of the cucurbitacin family, has been isolated as an active component from the root of Hemsleya amabilis (Cucurbitaceae), an ancient Chinese remedy for bacillary dysentery, gastroenteritis, and cancers. While the toxicity of other cucurbitacins has been explored in several cancers, little data exist on the effect of DHCF on human cancers, including prostate cancer (PCa). In this study, we explore the level and mechanisms of DHCF toxicity on human PCa cell lines. METHODS: Human PCa DU145, PC3, and LNCaP cells were treated with graded doses of DHCF in vitro, and anti-proliferative, cytotoxic, and proteomic effects were determined using MTS assay, cell cycle analysis, immunofluorescent staining, and western blotting. RESULTS: DHCF inhibited cell growth and induced cell cycle arrest at G(2)/M phase, formation of binucleated cells, and increased levels of apoptosis in all PCa cell lines tested. G-actin depletion, actin aggregation, and rod-like actin fibers, with little effect on microtubule structure, were observed after DHCF treatment. Actin aggregation and cofilin-actin rod formation were highly correlated with rapid and persistent dephosphorylation of cofilin-1 (cofilin). DHCF treatment resulted in upregulation of p21(Cip1) and downregulation of cyclin A in all three PCa cell lines. CONCLUSIONS: The anti-proliferative activity of DHCF on human PCa cells may be brought about by inducing actin aggregation and cofilin-actin rod formation, leading to cell cycle arrest, cytokinesis failure, and apoptosis" |
| Keywords: | "Actin Depolymerizing Factors/metabolism Actins/*metabolism Apoptosis/drug effects Cell Line, Tumor Cell Proliferation/*drug effects Cucurbitaceae/chemistry Cucurbitacins/isolation & purification/*pharmacology Cyclin A/genetics Cyclin-Dependent Kinase Inhi;" |
| Notes: | "MedlineRen, Shuai Ouyang, Dong-Yun Saltis, Mark Xu, Li-Hui Zha, Qing-Bing Cai, Ji-Ye He, Xian-Hui eng Research Support, Non-U.S. Gov't Germany 2012/07/21 Cancer Chemother Pharmacol. 2012 Sep; 70(3):415-24. doi: 10.1007/s00280-012-1921-z. Epub 2012 Jul 20" |
