title: Cytotoxic effect of s-petasin and iso-s-petasin on the proliferation of human prostate cancer cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C.
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Jou-Chun
authors.initials: JC
authors.lastname: Chou
authors.affiliation: Department of Physiology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Terry Fox Cancer Research Lab, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.affiliation: Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC Department of Health and Nutrition Biotechnology, College of Health Science, Asia University, Taichung, Taiwan, R.O.C. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Guei-Jane
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC Medical Center of Aging Research, China Medical University Hospital, Taichung, Taiwan, R.O.C. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan, R.O.C. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pharmacology, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C. swwang@mail.cgu.edu.tw.
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms; D012717:Sesquiterpenes / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D012717:Sesquiterpenes; C418727:petasin
keywords: Petasin; anti-proliferative; apoptosis; prostate cancer