The melanocortin signaling cAMP axis accelerates repair and reduces mutagenesis of platinum-induced DNA damage.
Sci Rep 2017 Sep 15;7(1):11708. Epub 2017 Sep 15.
The Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage. Read More