Zhi-Hong Wang1, Hui-Wen Hsu2, Jou-Chun Chou1, Ching-Han Yu3, Da-Tian Bau4, Guei-Jane Wang5, Chih-Yang Huang6, Paulus S Wang7, Shyi-Wu Wang8. 1. 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. 2. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. 3. 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. 4. Terry Fox Cancer Research Lab, China Medical University Hospital, Taichung, Taiwan, R.O.C. 5. 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. 6. Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan, ROC. 7. 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. 8. Department of Physiology and Pharmacology, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C. swwang@mail.cgu.edu.tw.
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. 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. Copyright
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. Copyright