Oxidative stress involvement in Physalis angulata-induced apoptosis in human oral cancer cells |
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Authors: | H-Z Lee W-Z Liu W-T Hsieh F-Y Tang J-G Chung Henry W-C Leung |
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Institution: | 1. School of Pharmacy, China Medical University, 91, Hsueh-Shih Road, Taichung 40402, Taiwan;2. Department of Pharmacology, China Medical University, Taichung, Taiwan;3. Department of Nutrition, China Medical University, Taichung, Taiwan;4. Department of Microbiology, China Medical University, Taichung, Taiwan;5. Department of Radiation Oncology, Chi Mei Hospital, Liouying, Tainan, Taiwan |
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Abstract: | In this report, we investigated the role of oxidative stress in Physalis angulata-induced apoptosis of human oral cancer cells. P. angulata-induced apoptosis was characterized by nuclear morphological changes, membrane blebbing and activation of caspase-9. Exposure of HSC-3 cells to P. angulata caused production of reactive oxygen species and up-regulation of oxidative stress markers heme oxygenase-1 (HO-1), superoxide dismutase (SOD), heat shock protein 70 (HSP70) and caspase-4. Down-regulation of HO-1, SOD and HSP70 proteins expression by attenuation of oxidative stress, pretreatment with glutathione or N-acetylcysteine, significantly decreased P. angulata-triggered cell death. The present study also demonstrated that the mitochondria and the endoplasmic reticulum are the targets of P. angulata in HSC-3 cells. Our results revealed that: (1) reactive oxygen species may play a dominant role in this process, (2) P. angulata induces oxidative stress in HSC-3 cells, (3) P. angulata-initiated apoptosis is caused through oxidative stress-dependent induction of heme oxygenase-1, Cu/Zn SOD and HSP70 proteins expression and (4) antioxidants inhibited P. angulata-induced cell death through inhibition of the proteins expression of HO-1, Cu/Zn SOD and HSP70. |
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Keywords: | AIF apoptosis-inducing factor HSC-3 cells human oral cancer cell line DAPI 4&prime 6-diamidino-2-phenylindole dihydrochloride DMEM Dulbecco&rsquo s modified Eagle&rsquo s medium DMSO dimethylsulfoxide DTT dithiothreitol EGTA ethylene glycol bis(β-aminoethylether)-N N N&prime N&prime -tetraacetic acid HEPES 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid HSP heat shock protein IgG immunoglobulin JC-1 5 5&prime 6 6&prime -tetrachloro-1 1&prime 3 3&prime -tetraethylbenzimidazolocarbocyanine iodide MTT 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide PAGE polyacrylamide gel electrophoresis PBS phosphate-buffered saline PI propidium iodide PMSF phenylmethylsulfonyl fluoride ROS reactive oxygen species SDS sodium dodecyl sulfate SOD superoxide dismutase |
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