Section Review Oncologic, Endocrine & Metabolic: Protein kinase C inhibitors as inducers of apoptosis for cancer therapy

Abstract

The antitumour activity of many chemotherapeutic agents is a consequence of their induction of apoptosis. Apoptosis represents an active, energy dependent process in which the cell participates in its own destruction. Recent investigations into the elements that regulate apoptosis have provided evidence for the existence of a balance between pro- and anti-apoptotic signalling. This balance appears to be reciprocally regulated through the sphingomyelin signal transduction pathway that mediates the pro-apoptotic signals, and the activation of the phosphoinositide-protein kinase C (PKC) pathway that mediates the anti-apoptotic signals. Thus, inhibition of the phosphoi-nositide-PKC pathway by PKC specific inhibitors may be sufficient to tip the balance in favour of pro-apoptotic signals. Consequently, PKC presents a novel target for anti-cancer therapy. Members of the PKC family are characterised by a unique amino-terminal regulatory domain, which contains the phorbol ester binding site, and a car-boxyl-termi...