Characterization of calcium release-activated apoptosis of LNCaP prostate cancer cells

Apoptosis inhibition rather than enhanced cellular proliferation occurs in prostate cancer (CaP), the most commonly diagnosed malignancy in American men. Therefore, it is important to characterize residual apoptotic pathways in CaP cells. When intracellular Ca2+ stores are released and plasma membrane "store-operated" Ca2+ entry channels subsequently open, cytosolic [Ca2+] increases and is thought to induce apoptosis, However, cells incapable of releasing Ca2+ stores are resistant to apoptotic stimuli, indicating that Ca2+ store release is also important. We investigated whether release of intracellular Ca2+ stores is sufficient to induce apoptosis of the CaP cell line LNCaP. We developed a method to release stored Ca2+ without elevating cytosolic [Ca2+]; this stimulus induced LNCaP cell apoptosis, We compared the apoptotic pathways activated by intracellular Ca2+ store release with the dual insults of store release and cytosolic [Ca2+] elevation. Earlier processing of caspases-3 and -7 occurred when intracellular store release was the sole Ca2+ perturbation. Apoptosis was attenuated in both conditions in stable transfected cells expressing antiapoptotic proteins Bclx(L) and catalytically inactive caspase-9, and in both scenarios inactive caspase-9 became complexed with caspase-7. Thus, intracellular Ca2+ store release initiates an apoptotic pathway similar to that elicited by the dual stimuli of cytosolic [Ca2+] elevation and intracellular store release.