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

Abstract.

Background: The effects of the anti-anginal drug fendiline on intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in human PC3 prostate cancer cells were examined. Methods: [Ca²⁺]_i was measured using the fluorescent dye fura-2. Results: Fendiline (0.5–100 µM) increased [Ca²⁺]_i in a concentration-dependent manner. Ca²⁺ removal partly inhibited the Ca²⁺ signals. In Ca²⁺-free medium, pretreatment with 100 µM fendiline inhibited most of the [Ca²⁺]_i increase induced by 1 µM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor), and pretreatment with thapsigargin abolished the fendiline-induced [Ca²⁺]_i increases. Adding 3 mM Ca²⁺ increased [Ca²⁺]_i in cells pretreated with 0.5–200 µM fendiline in Ca²⁺-free medium. Pretreatment with 1 µM U73122 to block the formation of inositol-1,4,5-trisphosphate (IP₃) did not alter fendiline-induced internal Ca²⁺ release. Conclusions: The anti-anginal 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 of prostate cancer cells should be investigated.