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

Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca concentration ([Ca ]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250-1000 μM) caused [Ca ]i rises which was reduced by Ca removal. Treatment with thapsigargin eliminated diosgenin-induced [Ca ]i increases. In contrast, incubation with diosgeninabolished thapsigargin-caused [Ca ]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin-caused [Ca ]i increases. Diosgenin evoked Mn influx suggesting that diosgenin induced Ca entry. Diosgenin-induced Ca 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 Ca with BAPTA/AM. Together, diosgenin evoked [Ca ]i increases via Ca release and Ca influx, and caused Ca -non-associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer.