title: The P450 system and mTORC1 signalling in acne.
abstract: In this issue, Hellmann-Regen et al. suggested that anti-acne effects of erythromycin and tetracyclines may be related to their inhibitory effect of cytochrome P450-mediated degradation of all-trans-retinoic acid (ATRA). We have recently proposed that all anti-acne agents function by attenuation of increased mTORC1 signalling. This commentary links the P450 system to mTORC1 regulation in acne. Drug-mediated induction of P450 activity or P450 mutants with increased catabolic activity may reduce cellular ATRA levels and FoxO1 expression, thus reducing FoxO-mediated mTORC1 inhibition. In contrast, agents blocking ATRA degradation such as erythromycin and tetracyclines may improve acne by increasing FoxO1 expression with consecutive inhibition of mTORC1 signalling.
authors.affiliation: Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, Osnabrück, Germany.
authors.forename: Bodo C
authors.initials: BC
authors.lastname: Melnik
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy*; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D013754:Tetracyclines / Q000494:pharmacology*; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D013754:Tetracyclines; D014212:Tretinoin; D004917:Erythromycin
keywords: FoxO1; acne; androgens; cytochrome P450; mTORC1; retinoic acid