Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria‐dependent pathway in human osteosarcoma U‐2 OS cells |
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Authors: | Wen‐Wen Huang Yu‐Jen Chiu Ming‐Jen Fan Hsu‐Feng Lu Hsiu‐Feng Yeh Kun‐Hong Li Po‐Yuan Chen Jing‐Gung Chung Jai‐ Sing Yang |
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Affiliation: | 1. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;2. School of Medicine, China Medical University, Taichung, Taiwan;3. Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan;4. Department of Restaurant, Hotel and Institutional Management, Fu‐Jen Catholic University, Taipei, Taiwan;5. Department of Clinical Pathology, Cheng‐Hsin General Hospital, Taipei, Taiwan;6. School of Pharmacy, China Medical University, Taichung, Taiwan;7. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan |
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Abstract: | Kaempferol is a natural flavonoid. Previous studies have reported that kaempferol has anti‐proliferation activities and induces apoptosis in many cancer cell lines. However, there are no reports on human osteosarcoma. In this study, we investigate the anti‐cancer effects and molecular mechanisms of kaempferol in human osteosarcoma cells. Our results demonstrate that kaempferol significantly reduces cell viabilities of U‐2 OS, HOB and 143B cells, especially U‐2 OS cells in a dose‐dependent manner, but exerts low cytotoxicity on human fetal osteoblast progenitor hFOB cells. Comet assay, DAPI staining and DNA gel electrophoresis confirm the effects of DNA damage and apoptosis in U‐2 OS cells. Flow cytometry detects the increase of cytoplasmic Ca2+ levels and the decrease of mitochondria membrane potential. Western blotting and fluorogenic enzymatic assay show that kaempferol treatment influences the time‐dependent expression of proteins involved in the endoplasmic reticulum stress pathway and mitochondrial signaling pathway. In addition, pretreating cells with caspase inhibitors, BAPTA or calpeptin before exposure to kaempferol increases cell viabilities. The anti‐cancer effects of kaempferol in vivo are evaluated in BALB/cnu/nu mice inoculated with U‐2 OS cells, and the results indicate inhibition of tumor growth. In conclusion, kaempferol inhibits human osteosarcoma cells in vivo and in vitro. |
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Keywords: | Apoptosis Endoplasmic reticulum stress Kaempferol Mitochondria‐dependent U‐2 OS |
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