Involvement of protein kinase C δ (PKCδ) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells -: Lack of proteolytic cleavage of PKCδ

Phorbol esters, the activators of protein kinase C (PKC), induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. The role of individual PKC isozymes as mediators of this effect has not been thoroughly examined to date. To study the involvement of the novel isozyme PRC delta we used a replication-deficient. adenovirus (PKC delta AdV), which allowed for a tightly controlled expression of PKC delta in LNCaP cells. A significant reduction in cell number was observed after infection of LNCaP cells with PKC delta AdV. Overexpression of PKC delta markedly enhanced the apoptotic effect of phorbol 12-myristate 13-acetate in LNCaP cells. PKC delta-mediated apoptosis was substantially reduced by the pan-caspase inhibitor z-VAD and by Bcl-2 overexpression. Importantly, and contrary to other cell types, PKC delta-mediated apoptosis does not involve its proteolytic cleavage by caspase-3, suggesting that allosteric activation of PHC delta is sufficient to trigger apoptosis in LNCaP cells. In addition, phorbol ester-induced apoptosis was blocked by a kinase-deficient mutant of PHC delta, supporting the concept that PKC delta plays an important role in the regulation of apoptotic cell death in LNCaP prostate cancer cells.