Crude extract of Euphorbia formosana induces apoptosis of DU145 human prostate cancer cells acts through the caspase‐dependent and independent signaling pathway |
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| Authors: | Jiun‐Long Yang Jin‐Cherng Lien Ya‐Yin Chen Shu‐Chun Hsu Shu‐Jen Chang An‐Cheng Huang Sakae Amagaya Shinji Funayana W. Gibson Wood Chao‐Lin Kuo Jing‐Gung Chung |
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| Affiliation: | 1. Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan;2. Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan;3. Department of Chinese‐Western Medicine Integration, Chung Shan Medical University Hospital, Taichung, Taiwan;4. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;5. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;6. School of Pharmacy, China Medical University, Taichung, Taiwan;7. Department of Nursing, St. Mary's Medicine Nursing and Management College, Yilan, Taiwan;8. Department of Kampo Pharmaceutical Sciences, Nihon Pharmaceutical University, Saitama, Japan;9. Department of Medicinal Chemistry, Nihon Pharmaceutical University, Saitama, Japan;10. Department of Pharmacology, University of Minnesota, School of Medicine, Geriatric Research, Education and Clinical Center, VA Medical Center, Minneapolis, Minnesota, USA;11. Department of Biotechnology, Asia University, Taichung, Taiwan |
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| 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 ΔΨm levels. 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. |
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| Keywords: | crude extract of Euphorbia formosana (CEEF) DU145 human prostate cancer cells cell cycle apoptosis mitochondria |
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