Involvement of protein kinase C delta (PKC delta) in phorbol ester-inducedapoptosis in LNCaP prostate cancer cells - Lack of proteolytic cleavage ofPKC delta

Phorbol esters, the activators of protein kinase C (PKC), induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. The role of individual P KC 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 re plication-deficient. adenovirus (PKC delta AdV), which allowed for a tightl y controlled expression of PKC delta in LNCaP cells. A significant reductio n 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 apoptos is 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.