Phorbol ester-induced apoptosis and senescence in cancer cell models

Protein kinase C (PKC) isozymes catalyze the phosphorylation of substrates that play key roles in the control in proliferation, differentiation, and survival. Treatment of cells with phorbol esters, activators of classical and novel PKC isozymes, leads to a plethora of responses in a strict cell-type-dependent specific manner. Interestingly, a few cell models undergo apoptosis in response to phorbol ester stimulation, including androgen-dependent prostate cancer cells. This effect involves the autocrine secretion of death factors and activation of the extrinsic apoptotic cascade. We have recently found that in other models, such as lung cancer cells, phorbol esters lead to irreversible growth arrest and senescence. This chapter describes the methods we use to assess these phorbol ester responses in cancer cell models, focusing on apoptosis and senescence.