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.
Original language | English |
---|---|
Pages (from-to) | 395-403 |
Number of pages | 9 |
Journal | Environmental Toxicology |
Volume | 35 |
Issue number | 3 |
DOIs | |
State | Published - 01 03 2020 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2019 Wiley Periodicals, Inc.
Keywords
- Ca handling
- cytotoxicity
- diosgenin
- endoplasmic reticulum
- prostate cancer cell