Effect of [10]-Gingerol on [Ca2+]i and Cell Death in Human Colorectal Cancer Cells

The effect of [10]-gingerol on cytosol free Ca2+ concentration ([Ca2+](i)) and viability is large unknown. This study examines the early signaling effects of [10]-gingerol on human colorectal cancer cells. It was found that this compound caused a slow and sustained rise of [Ca2+](i) in a concentration-dependent manner. [10]-Gingerol also induced a [Ca2+](i) rise when extracellular Ca2+ was removed, but the magnitude was reduced by 38%. In a Ca2+-free medium, the [10]-gingerol- induced [Ca2+](i) rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). The elevation of [10]-gingerol- caused [Ca2+](i) in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [10]-gingerol- induced Ca2+ influx was insensitive to L-type Ca2+ channel blockers. At concentrations of 10-100 mu M, [10]-gingerol killed cells in a concentration-dependent manner. These findings suggest that [10]-gingerol induces [Ca2+](i) rise by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from non-L- type Ca2+ channels in SW480 cancer cells.