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.