title: Crude extract of Euphorbia formosana induces apoptosis of DU145 human prostate cancer cells acts through the caspase-dependent and independent signaling pathway.
abstract: Prostate cancer is the most frequently diagnosed malignancy in men and the second highest contributor of male cancer mortality. The crude extract of Euphorbia formosana (CEEF) has been used for treatment of different diseases but the cytotoxic effects of CEEF on human cancer cells have not been reported. The purpose of the present experiments was to determine effects of CEEF on cell cycle distribution and induction of apoptosis in DU145 human prostate cancer cells in vitro. Contrast-phase microscope was used for examining cell morphological changes. Flow cytometric assays were used for cell viability, cell cycle, apoptosis, reactive oxygen species, and Ca2+production and mitochondria membrane potential (ΔΨm). Western blotting was used for examining protein expression of cell cycle and apoptosis associated proteins. Real-time PCR was used for examining mRNA levels of caspase-3, -8, and -9, AIF, and Endo G. Confocal laser microscope was used to examine the translocation of AIF, Endo G, and cytochrome in DU145 cells after CEEF exposure. CEEF-induced cell morphological changes, decreased the percentage of viable cells, and induced S phase arrest and apoptosis in DU145 cells. Furthermore, CEEF promoted RAS and Ca2+production and reduced ΔΨmlevels. Real-time QPCR confirmed that CEEF promoted the mRNA expression of caspase-3 and -9, AIF and Endo G and we found that AIF and Endo G and cytochrome c were released from mitochondria. Taken together, CEEF-induced cytotoxic effects via ROS production, induced S phase arrest and induction of apoptosis through caspase-dependent and independent and mitochondria-dependent pathways in DU245 cancer cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1600-1611, 2016.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jiun-Long
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Lien
authors.affiliation: Department of Chinese-Western Medicine Integration, Chung Shan Medical University Hospital, Taichung, 402, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan.
authors.forename: Ya-Yin
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan, 266, Taiwan.
authors.forename: An-Cheng
authors.initials: AC
authors.lastname: Huang
authors.affiliation: Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, Saitama, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Amagaya
authors.affiliation: Department of Medicinal Chemistry, Nihon Pharmaceutical University, Saitama, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Funayana
authors.affiliation: Department of Pharmacology, University of Minnesota, School of Medicine, Geriatric Research, Education and Clinical Center, VA Medical Center, Minneapolis, Minnesota, 55455, USA.
authors.forename: W Gibson
authors.initials: WG
authors.lastname: Wood
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan. jgchung@mail.cmu.edu.tw.
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan. clclkuo@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan. clclkuo@mail.cmu.edu.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D028481:Euphorbia; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D020169:Caspases
keywords: DU145 human prostate cancer cells; apoptosis; cell cycle; crude extract of Euphorbia formosana (CEEF); mitochondria