Mitochondria, metabolism and cancer: a growing role in cancer cell differentiation and cancer cell dormancy

Background It is well known that physical or chemical agents can induce cell differentiation, or better pseudo-differentiation, in different human tumor cell lines. As an example, we cite the synthetic ligands of Peroxisome Proliferators Activated Receptors (PPARs), a very heterogeneous class of chemical with numerous biological activities which are mainly reported for their capacity to bind and activate this particular class of nuclear receptors. PPARs are involved in lipid and glucidic metabolism, immune regulation, cancer cell differentiation and, paradoxically, cancer induction. As a matter of fact, some synthetic PPARligands have been already employed in pharmacotherapy and all showed intriguing pharmacotoxicological profiles. A re-evaluation of the biological activities of PPARs synthetic ligands, in particular of the induced mitochondrial dysfunction based on a rotenone-like Complex I partial inhibition and of its consequent metabolic adaptations seems to shed new light on dedifferentiation/ differentiation processes in cancer and above all in cancer cell dormancy.