Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 humanprostate cancer cells

Background: The effects of the anti-anginal drug fendiline on intracellular Ca2+ concentrations ([Ca2+](i)) in human PC3 prostate cancer cells were ex amined. Methods: [Ca2+](i) was measured using the fluorescent dye fura-2. R esults: Fendiline (0.5-100 muM) increased [Ca2+](i) in a concentration-depe ndent manner.. signals. In Ca2+ removal partly inhibited the Ca2+ Ca2+-free medium pretreatment with 100 muM fendiline inhibited most of the [Ca2+](i) increase induced by I muM thapsigargin (an endoplasmic reticulum Ca pump i nhibitor), and pretreatment with thapsigargin abolished the fendiline-induc ed [Ca2+](i) increases. Adding 3 mM Ca2+ increased [Ca2+](i) in cells pretr eated with 0.5-200 muM fendiline in Ca2+-free medium. Pretreatment with I m uM U73122 to block the formation of inositol-1,4,5-trisphosphate (IP3) did not alter fendiline-induced internal Ca2+ release. Conclusions: The anti-an ginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+](i) may lead to cell injury and death , the long-term effect of fendiline on the function or prostate cancer cell s should be investigated.