Protein kinase C as a target for new anti-cancer agents

Abstract

Cancer joins the category of diseases involving abnormalities in the rate of proliferation of cells and is associated with uncontrolled cell division, where cells either generate their own growth-promoting stimuli or neighboring cells or do not respond to growth inhibitory signals. Protein kinase C (PKC) is one of the key elements in the tumor growth signal transduction pathways and is found to be overexpressed in several malignant cell types. A way to control cell proliferation and cell differentiation is by influencing signal transduction pathways by modulation of PKC. PKC encloses 12 different isoenzymes, and each isoenzyme is found to have a different functional property. Because specific PKC isoenzyme types are present in different (malignant) cell species, they may be an attractive target in the development of anti-cancer agents. Classification and identification of the available PKC isoenzymes in different tumor cells could be useful in targeting specific tumors. PKC also tends to be overexpressed in association with the multidrug resistance pheno-type. This concise review deals with the role of PKC isoenzymes in (tumor) cell biology and evaluates the antineoplastic agents interacting on PKC isoenzymes.