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

Abstract

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 Ca 2+ concentration ([Ca 2+ ]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250‐1000 μM) caused [Ca 2+ ]i rises which was reduced by Ca 2+ removal. Treatment with thapsigargin eliminated diosgenin‐induced [Ca 2+ ]i increases. In contrast, incubation with diosgeninabolished thapsigargin‐caused [Ca 2+ ]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin‐caused [Ca 2+ ]i increases. Diosgenin evoked Mn 2+ influx suggesting that diosgenin induced Ca 2+ entry. Diosgenin‐induced Ca 2+ 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 2+ with BAPTA/AM. Together, diosgenin evoked [Ca 2+ ]i increases via Ca 2+ release and Ca 2+ influx, and caused Ca 2+ ‐non‐associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer.