Resveratrol induces apoptosis of human nasopharyngeal carcinoma cells via activation of multiple apoptotic pathways.
Resveratrol, a naturally occurring dietary compound with chemopreventive properties has been reported to trigger a variety of cancer cell types to apoptosis. Whether resveratrol shows any activity on human nasopharyngeal carcinoma (NPC) cells remained to be determined. The aim of this study was to investigate the effect and mechanism of resveratrol on human NPC cells. Treatment of resveratrol resulted in significant decrease in cell viability of NPC cell lines in a dose- and time-dependent manner. A dose-dependent apoptotic cell death was also measured by flow cytometery analysis. Molecular mechanistic studies of apoptosis unraveled resveratrol treatment resulted in a significant loss of mitochondrial transmembrane potential, release of cytochrome c, enhanced expression of Fas ligand (FasL), and suppression of glucose-regulated protein 78 kDa (GRP78). These were followed by activation of caspases-9, -8, -4, and -3, subsequently leading to DNA fragmentation and cell apoptosis. Furthermore, up-regulation of proapoptotic Bax and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, resveratrol induces apoptosis in human NPC cells through regulation of multiple apoptotic pathways, including death receptor, mitochondria, and endoplasmic reticulum (ER) stress. Resveratrol can be developed as an effective compound for human NPC treatment.
Huang
Tsung-Teng
TT
Department of Life Science, National Central University, and Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, Republic of China.
Lin
Hung-Chi
HC
Chen
Chang-Chieh
CC
Lu
Chia-Chen
CC
Wei
Chia-Fong
CF
Wu
Ting-Shu
TS
Liu
Fu-Guo
FG
Lai
Hsin-Chih
HC
D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D053222:Fas Ligand Protein; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D051742:Transcription Factor CHOP; D020169:Caspases; D000077185:Resveratrol