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

Abstract

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 mM, [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.