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

10.4077/CJP.2017.BAG506

Chi-Ting Horng；Chiang-Ting Chou；Te-Kung Sun；Wei-Zhe Liang；Chun-Chi Kuo；Jue-Long Wang；Pochuen Shieh；Chung-Ren Jan

Ca^(2+) ； carvacrol ； endoplasmic reticulum ； human prostate cancer cells ； store-operated Ca^(2+) channels

The Chinese Journal of Physiology

60卷5期（2017 / 10 / 31）

275 - 283

英文

Carvacrol, a monoterpenic phenol compound, has been shown to possess various biological effects in different models. However, the effect of carvacrol on intracellular Ca^(2+) and its related physiology in human prostate cancer is unknown. This study explored the effect of carvacrol on cytosolic free Ca^(2+) levels ([Ca^(2+)]_i) and viability in PC3 human prostate cancer cells. Fura-2, a Ca^(2+)- sensitive fluorescent dye, was used to assess [Ca^(2+)]i. Cell viability was measured by the detecting reagent WST-1. Carvacrol at concentrations of 200-800 μM caused [Ca^(2+)]_i rises in a concentration-dependent manner. Removal of extracellular Ca^(2+) reduced carvacrol's effect by approximately 60%. Carvacrol-induced Ca^(2+) entry was confirmed by Mn^(2+) entry-induced quench of fura-2 fluorescence, and was inhibited by approximately 30% by 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 (TG) abolished carvacrol-induced [Ca^(2+)]_i rises. Treatment with carvacrol also abolished TG-induced [Ca^(2+)]_i rises. Carvacrol-induced Ca^(2+) release from the endoplasmic reticulum was abolished by inhibition of phospholipase C (PLC). Carvacrol killed cells at concentrations of 200-600 μM in a concentration-dependent fashion. Chelating cytosolic Ca^(2+) with BAPTA/AM did not prevent carvacrol's cytotoxicity. Together, in PC3 cells, carvacrol 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. Carvacrol also induced Ca^(2+)-dissociated cell death.

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