Effect of BayK 8644 on [Ca²⁺]i and viability in PC3 human prostate cancer cells.
The effect of BayK 8644 on cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and viability in PC3 human prostate cancer cells was explored. Fura-2 was applied to measure [Ca²⁺]i. BayK 8644 at 1-50 μM induced a [Ca2²⁺]i rise concentration-dependently. The response was reduced by removing extracellular Ca²⁺. BayK 8644-evoked Ca²⁺ entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In Ca²⁺-free medium, incubation with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished BayK 8644-induced [Ca²⁺]i rise. Inhibition of phospholipase C did not alter BayK 8644-induced [Ca²⁺]i rise. BayK 8644 killed cells in a concentrationdependent manner, which was not reversed by chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Collectively, in PC3 human prostate cancer cells, BayK 8644 induced a [Ca²⁺]i rise by evoking phospholipase C-independent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via protein kinase C-sensitive store-operated Ca²⁺ channels (and/or T-type Ca²⁺ channels). At high concentrations, BayK 8644 caused cell death.
School of Pharmacy, College of Pharmacy, China Medical University, Taichung 43302, Taiwan, Republic of China.
Zhen-Rung
ZR
Lai
Chiang-Ting
CT
Chou
Shiuh-Inn
SI
Liu
Wei-Zhe
WZ
Liang
Jong-Khing
JK
Huang
Chung-Ren
CR
Jan
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology
D002120:Calcium Channel Agonists; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium