PMID- 26717916 OWN - NLM STAT- MEDLINE DCOM- 20161223 LR - 20190402 IS - 0304-4920 (Print) IS - 0304-4920 (Linking) VI - 58 IP - 6 DP - 2015 Dec 31 TI - Effect of Miconazole on [Ca(2)(+)]i and Cytotoxicity in ZR-75-1 Human Breast Cancer Cells. PG - 377-84 LID - CJP.2015.BAD347 [pii] LID - 10.4077/CJP.2015.BAD347 [doi] AB - The effect of the antifungal drug miconazole on Ca(2)(+) signaling in human breast cancer cells is unknown. This study examined the effect of miconazole on cytosolic free Ca(2)(+) concentrations ([Ca(2)(+)]i) in ZR-75-1 human breast cancer cells. The Ca(2)(+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2)(+)]i. Miconazole induced [Ca(2)(+)]i rises concentration-dependently. The response was reduced by 60% by removing extracellular Ca(2)(+). Miconazole-induced Ca(2)(+) entry was abolished by the protein kinase C (PKC) inhibitor GF109203X, and nifedipine, but was insensitive to econazole, SKF96365 and the protein kinase C activator phorbol 12-myristate 13 acetate (PMA). In Ca(2)(+)-free medium, treatment with the endoplasmic reticulum Ca(2)(+) pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) or thapsigargin (TG) greatly inhibited miconazole-evoked [Ca(2)(+)]i rises. Conversely, treatment with miconazole abolished TG and BHQ-evoked [Ca(2)(+)]i rises. Inhibition of phospholipase C (PLC) with U73122 abolished miconazole-induced [Ca(2)(+)]i rises. At concentrations of 30-50 muM, micronazole killed cells in a concentration-dependent manner. This cytotoxic effect was not reversed by chelating cytosolic Ca(2)(+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Together, in ZR-75-1 cells, miconazole induced [Ca(2)(+)]i rises by evoking PLC-dependent Ca(2)(+) release from the endoplasmic reticulum, and PKC-regulated nifedipine-sensitive Ca(2)(+) entry. Miconazole-caused cell death was not triggered by a preceding [Ca(2)(+)]i rise. FAU - Roan, Cherng-Jau AU - Roan CJ AD - Department of Obstetrics and Gynecology, E-DA Hospital, Kaohsiung 82445, Taiwan, Republic of China. FAU - Chou, Chiang-Ting AU - Chou CT AD - Department of Nursing, Division of Basic Medical Sciences, Chang Gung Institute of Technology, Chia-Yi 61363, Taiwan, Republic of China. AD - Chronic Diseases and Health Promotion Research Center, Chang Gung Institute of Technology, Chia-Yi 61363, 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 - Chang, Hong-Tai AU - Chang HT AD - Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China. FAU - Kuo, Daih-Huang AU - Kuo DH AD - Department of Pharmacy, Tajen University, Pingtung 90741, 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 - Chen, Fu-An AU - Chen FA AD - Department of Pharmacy, Tajen University, Pingtung 90741, 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 Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - India TA - Chin J Physiol JT - The Chinese journal of physiology JID - 7804502 RN - 7NNO0D7S5M (Miconazole) RN - EC 3.1.4.- (Type C Phospholipases) RN - SY7Q814VUP (Calcium) SB - IM MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Calcium/*metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Miconazole/*pharmacology MH - Type C Phospholipases/physiology EDAT- 2016/01/01 06:00 MHDA- 2016/12/24 06:00 CRDT- 2016/01/01 06:00 PHST- 2016/01/01 06:00 [entrez] PHST- 2016/01/01 06:00 [pubmed] PHST- 2016/12/24 06:00 [medline] AID - CJP.2015.BAD347 [pii] AID - 10.4077/CJP.2015.BAD347 [doi] PST - ppublish SO - Chin J Physiol. 2015 Dec 31;58(6):377-84. doi: 10.4077/CJP.2015.BAD347.