Effect of Thymol on Ca^(2+) Homeostasis and Viability in PC3 Human Prostate Cancer Cells

10.4077/CJP.2017.BAF447

Jeng-Hsien Yeh；Chiang-Ting Chou；I-Shu Chen；Ti Lu；Ko-Long Lin；Chia-Cheng Yu；Wei-Zhe Liang；Hong-Tai Chang；Chun-Chi Kuo；Chin-Man Ho；Wen-Teng Chang；Pochuen Shieh；Chung-Ren Jan

Ca^(2+) ； endoplasmic reticulum ； fura-2 ； prostate cancer cells ； thymol

The Chinese Journal of Physiology

60卷1期（2017 / 02 / 28）

32 - 40

英文

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

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