Effect of BayK 8644 on [Ca ²⁺ ] _i and viability in PC3 human prostate cancer cells

The effect of BayK 8644 on cytosolic Ca ²⁺ concentrations ([Ca ²⁺ ] _i ) and viability in PC3 human prostate cancer cells was explored. Fura-2 was applied to measure [Ca ²⁺ ] _i . BayK 8644 at 1-50 μM induced a [Ca ²⁺ ] _i rise concentration-dependently. The response was reduced by removing extracellular Ca ²⁺ . BayK 8644-evoked Ca ²⁺ entry was inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators. In Ca ²⁺ -free medium, incubation with the endoplasmic reticulum Ca ²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished BayK 8644-induced [Ca ²⁺ ] _i rise. Inhibition of phospholipase C did not alter BayK 8644-induced [Ca ²⁺ ] _i rise. BayK 8644 killed cells in a concentrationdependent manner, which 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). Collectively, in PC3 human prostate cancer cells, BayK 8644 induced a [Ca ²⁺ ] _i rise by evoking phospholipase C-independent Ca ²⁺ release from the endoplasmic reticulum and Ca ²⁺ entry via protein kinase C-sensitive store-operated Ca ²⁺ channels (and/or T-type Ca ²⁺ channels). At high concentrations, BayK 8644 caused cell death.