Exploring the impact of a naturally occurring sapogenin diosgenin on underlying mechanisms of Ca2+ movement and cytotoxicity in human prostate cancer cells.

Abstract

Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca2+ concentration ([Ca2+ ]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250-1000 μM) caused [Ca2+ ]i rises which was reduced by Ca2+ removal. Treatment with thapsigargin eliminated diosgenin-induced [Ca2+ ]i increases. In contrast, incubation with diosgeninabolished thapsigargin-caused [Ca2+ ]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin-caused [Ca2+ ]i increases. Diosgenin evoked Mn2+ influx suggesting that diosgenin induced Ca2+ entry. Diosgenin-induced Ca2+ influx was suppressed by PMA, GF109203X, and nifedipine, econazole, or SKF96365. Diosgenin (250-600 μM) concentration-dependently decreased cell viability. However, diosgenin-induced cytotoxicity was not reversed by chelation of cytosolic Ca2+ with BAPTA/AM. Together, diosgenin evoked [Ca2+ ]i increases via Ca2+ release and Ca2+ influx, and caused Ca2+ -non-associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer.