Effect of Thymol on Ca2+ Homeostasis and Viability in PC3 Human Prostate Cancer Cells

Thymol is a phenolic compound that affects physiology in different cell models. However, whether thymol affects Ca2+ homeostasis in prostate cancer cells is unknown. The action of this compound on cytosolic Ca2+ concentrations ([Ca2+] i) and viability in PC3 human prostate cancer cells was explored. The results show that thymol at concentrations of 100-1500 mu M caused [Ca2+] i rises in a concentration-dependent manner. Removal of extracellular Ca2+ reduced thymol's effect by approximately 80%. Thymol-induced Ca2+ entry was confirmed by Mn2+ entry-induced quench of fura-2 fluorescence, and was inhibited by approximately 30% by Ca2+ entry modulators (nifedipine, econazole, SKF96365), and the protein kinase C (PKC) inhibitor GF109203X. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished thymol-induced [Ca2+](i) rises. Treatment with thymol also abolished thapsigargin-induced [Ca2+] i rises. Thymol-induced Ca2+ release from the endoplasmic reticulum was abolished by the phospholipase C (PLC) inhibitor U73122. Thymol at 100-900 mu M decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, thymol induced [Ca2+](i) rises by inducing PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ channels and other unknown channels. Thymol also induced Ca2+-dissociated cell death.