Protein kinase C α and δ are members of a large kinase family of high potential for novel anticancer targeted therapy

Protein kinase C (PKC) family enzymes participate in several cell-signaling pathways by controlling proliferation, differentiation, senescence, invasion, and apoptosis both in normal and in cancer cells. The PKC family consists of serine/threonine kinases including 12 isoforms, which could be divided in three groups based on their interactions with calcium and diacylglycerol. Studies have suggested that PKCs play a role in carcinogenesis and maintenance of malignant phenotype. Potentiation of malignant phenotype may be mediated by activation of selective PKC isoenzymes and/or through altered isoenzyme expression profile compared to the originating tissue. PKC-δ is thought to mediate anticancer effects and PKC-α has often been linked to malignant phenotype. During the past few years, preclinical and clinical data with first generation PKC inhibitors/ activators provided insights that PKCs may indeed represent attractive targets for the discovery of small molecules with new anticancer properties. This review focuses on current knowledge on regulation of PKC-δ and PKC-α in cancer progression highlighting the potential role of those kinases as targets for anticancer therapeutics.