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[摘要]：The effect of [6]-shogaol (1) on cytosolic free Ca2+ concentrations ([Ca2+](i)) and viability has not been explored previously in oral epithelial cells. The present study has examined whether 1 alters [Ca2+](i) and viability in OC2 human oral cancer cells. Compound 1 at concentrations >= 5 mu M increased [Ca2+](i) in a concentration-dependent manner with a 50% effective concentration (EC50) value of 65 mu M. The Ca2+ signal was reduced substantially by removing extracellular Ca2+. In a Ca2+-free medium, the 1-induced [Ca2+](i) elevation was mostly attenuated by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). The [Ca2+](i) signal was inhibited by La3+ but not by L-type Ca2+ channel blockers. The elevation of [Ca2+](i) caused by 1 in a Ca2+-containing medium was not affected by modulation of protein kinase C activity, but was inhibited by 82% with the phospholipase A2 inhibitor aristolochic acid I (20 mu M). U73122, a selective inhibitor of phospholipase C, abolished 1-induced [Ca2+](i) release. At concentrations of 5-100 mu M, 1 killed cells in a concentration-dependent manner. These findings suggest that [6]-shogaol induces a significant rise in [Ca2+](i) in oral cancer OC2 cells by causing stored Ca2+ release from the thapsigargin-sensitive endoplasmic reticulum pool in an inositol 1,4,5-trisphosphate-dependent manner and by inducing Ca2+ influx via a phospholipase A2- and La3+-sensitive pathway. |
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