PMID- 28950692 OWN - NLM STAT- MEDLINE DCOM- 20180313 LR - 20191210 IS - 0304-4920 (Print) IS - 0304-4920 (Linking) VI - 60 IP - 5 DP - 2017 Oct 31 TI - Effect of Carvacrol on Ca(2)(+) Movement and Viability in PC3 Human Prostate Cancer Cells. PG - 275-283 LID - CJP.2017.BAG506 [pii] LID - 10.4077/CJP.2017.BAG506 [doi] AB - 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 muM 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 muM 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. FAU - Horng, Chi-Ting AU - Horng CT AD - Department of Ophthalmology, Kaohsiung Armed Force General Hospital, Kaohsiung 80284, Taiwan, Republic of China. FAU - Chou, Chiang-Ting AU - Chou CT AD - Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China. AD - Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China. FAU - Sun, Te-Kung AU - Sun TK AD - Department of Pediatrics, St. Joseph Hospital, Kaohsiung 80288, Taiwan, Republic of China. FAU - Liang, Wei-Zhe AU - Liang WZ AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. FAU - Kuo, Chun-Chi AU - Kuo CC AD - Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China. FAU - Wang, Jue-Long AU - Wang JL AD - Department of Rehabilitation, Kaohsiung Veterans General Hospital Tainan Branch, Tainan 71051, Taiwan, Republic of China. FAU - Shieh, Pochuen AU - Shieh P AD - Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China. FAU - Jan, Chung-Ren AU - Jan CR AD - Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. LA - eng GR - VGHKS105-G01-1, VGHKS105-132/Kaohsiung Veterans General Hospital/International PT - Journal Article PL - India TA - Chin J Physiol JT - The Chinese journal of physiology JID - 7804502 RN - 0 (Cymenes) RN - 0 (Monoterpenes) RN - 9B1J4V995Q (carvacrol) RN - EC 3.1.4.- (Type C Phospholipases) RN - SY7Q814VUP (Calcium) SB - IM MH - Calcium/*metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cymenes MH - Humans MH - Male MH - Monoterpenes/*pharmacology MH - Prostatic Neoplasms/*drug therapy/metabolism/pathology MH - Type C Phospholipases/physiology OTO - NOTNLM OT - Ca(2)(+) OT - carvacrol OT - endoplasmic reticulum OT - human prostate cancer cells OT - store-operated Ca(2)(+) channels COIS- The authors declare that there are no conflicts of interests. EDAT- 2017/09/28 06:00 MHDA- 2018/03/14 06:00 CRDT- 2017/09/28 06:00 PHST- 2017/09/28 06:00 [pubmed] PHST- 2018/03/14 06:00 [medline] PHST- 2017/09/28 06:00 [entrez] AID - CJP.2017.BAG506 [pii] AID - 10.4077/CJP.2017.BAG506 [doi] PST - ppublish SO - Chin J Physiol. 2017 Oct 31;60(5):275-283. doi: 10.4077/CJP.2017.BAG506.