PT - JOURNAL ARTICLE AU - ZHI-HONG WANG AU - HUI-WEN HSU AU - JOU-CHUN CHOU AU - CHING-HAN YU AU - DA-TIAN BAU AU - GUEI-JANE WANG AU - CHIH-YANG HUANG AU - PAULUS S. WANG AU - SHYI-WU WANG TI - Cytotoxic Effect of <em>S</em>-Petasin and Iso-<em>S</em>-Petasin on the Proliferation of Human Prostate Cancer Cells DP - 2015 Jan 01 TA - Anticancer Research PG - 191--199 VI - 35 IP - 1 4099 - http://ar.iiarjournals.org/content/35/1/191.short 4100 - http://ar.iiarjournals.org/content/35/1/191.full SO - Anticancer Res2015 Jan 01; 35 AB - Background: Petasin (Petasides hybridus) is a perennial shrub that is found in Europe as well as parts of Asia and North America and is being used to treat hypertension, tumors and asthma. In a previous study, we reported that petasin possesses biological effects including inhibition of testosterone production and the release of corticosterone from rat zona fasciculata-reticularis cells, and anti-proliferative effect on human T24 bladder carcinoma cells. Materials and Methods: In the present study, we assessed the effects of S-petasin and iso-S-petasin on the growth and proliferation of two hormone-independent DU145 and PC3 and one hormone-dependent LNCaP prostate cancer cell line at concentrations of 10-7-10-5 mol/l. The cell proliferation index, cell number index, expression of caspases and apoptosis-associated proteins and cell morphology were measured. Results: S-Petasin and iso-S-petasin reduced the viable cell number and increased the numbers of apoptotic cells in the tested cell lines in a dose-dependent manner. Western blot analysis revealed that S-petasin and iso-S-petasin reduced the protein levels of procaspase 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase (PARP) in all tested prostate cancer cell lines, and reduced that of procaspase 7 in LNCaP and PC3 cells. At the same time, S-petasin and iso-S-petasin increased mitochondrial membrane permeability and cytochrome c release from mitochondria to the cytosol via reducing the ratio of BCL2/BAX in DU145 and PC3 cells, and up-regulating the levels of p53 in DU145 cells but down-regulating it in PC3 cells. Conclusion: These results indicate that S-petasin and iso-S-petasin induce apoptosis via the activation of mitochondria-related pathways in prostate cancer cells, suggesting S-petasin and iso-S-petasin could be potential anticancer agents.