Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells
| Autor: | Kun Hong Li, Hsiu Feng Yeh, Ming Jen Fan, Hsu Feng Lu, Jai Sing Yang, Po-Yuan Chen, Jing Gung Chung, Yu Jen Chiu, Wen Wen Huang |
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| Rok vydání: | 2010 |
| Předmět: |
Cell Survival
Cell Apoptosis Bone Neoplasms Biology Endoplasmic Reticulum Mice Random Allocation chemistry.chemical_compound Cell Line Tumor medicine Animals Anticarcinogenic Agents Humans DAPI Kaempferols Cell Proliferation Membrane Potential Mitochondrial Mice Inbred BALB C Osteosarcoma Cell growth Endoplasmic reticulum Caspase Inhibitors Xenograft Model Antitumor Assays Molecular biology Comet assay medicine.anatomical_structure chemistry Cell culture Comet Assay Kaempferol DNA Damage Signal Transduction Food Science Biotechnology |
| Zdroj: | Molecular Nutrition & Food Research. 54:1585-1595 |
| ISSN: | 1613-4125 |
| Popis: | 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 Ca(2+) 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/c(nu/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. |
| Databáze: | OpenAIRE |
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