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 G2/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 p21Cip1and 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.
Written by:
Ren S, Ouyang DY, Saltis M, Xu LH, Zha QB, Cai JY, He XH. Are you the author?
Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, 601 Huangpu Dadao West, Guangzhou, 510632, China.
Reference: Cancer Chemother Pharmacol. 2012 Sep;70(3):415-24.
doi: 10.1007/s00280-012-1921-z
PubMed Abstract
PMID: 22814677
UroToday.com Investigative Urology Section
