Effect of melamine on [Ca2+]i and viability in PC3 human prostate cancer cells

•Melamine induced [Ca2+]i rises in PC3 human prostate cancer cells.•Melamine evoked phospholipase C-independent Ca2+ release from the endoplasmic reticulum.•Melamine induced Ca2+ entry via store-operated Ca2+ channels.•Melamine decreased viability in a Ca2+-independent manner.

Melamine is thought to be an endocrine disrupter that affects physiology in cells. This study examined the effect of melamine on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells. Melamine evoked [Ca2+]i rises concentration-dependently. Melamine-evoked Ca2+ entry was inhibited by nifedipine, econazole, SKF96365, GF109203X and phorbol 12-myristate 13 acetate. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin inhibited melamine-evoked [Ca2+]i rise. Conversely, treatment with melamine abolished thapsigargin-evoked [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter melamine-evoked [Ca2+]i rise. Melamine at 500–800 μM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Collectively, our data suggest that in PC3 cells, melamine induced [Ca2+]i rises by evoking phospholipase C-independent Ca2+ release from the endoplasmic reticulum, and Ca2+ entry via protein kinase C-regulated store-operated Ca2+ entry. Melamine also caused Ca2+-independent cell death.