Effect of [10]-gingerol on [ca2+]i and cell death in human colorectal cancer cells.

The effect of [10]-gingerol on cytosol free Ca(2+) concentration (Ca(2+)) 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 Ca(2+) in a concentration-dependent manner. [10]-Gingerol also induced a Ca(2+) rise when extracellular Ca(2+) was removed, but the magnitude was reduced by 38%. In a Ca(2+)-free medium, the [10]-gingerol-induced Ca(2+) rise was partially abolished by depleting stored Ca(2+) with thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). The elevation of [10]-gingerol-caused Ca(2+) in a Ca(2+)-containing medium was not affected by modulation of protein kinase C activity. The [10]-gingerol-induced Ca(2+) influx was insensitive to L-type Ca(2+) channel blockers. At concentrations of 10-100 mM, [10]-gingerol killed cells in a concentration-dependent manner. These findings suggest that [10]-gingerol induces Ca(2+) rise by causing Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx from non-L-type Ca(2+) channels in SW480 cancer cells.