Exploring the impact of a naturally occurring sapogenin diosgenin on underlying mechanisms of Ca²⁺ 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 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.