Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid

A significant increase in tumor regression was induced in N-nitroso-N-methylurea-induced mammary tumors in rats treated with the combination of melatonin and 9-cis-retinoic acid (9cRA). Treatment groups included: control (ethanolic saline), 9cRA (30 mg/kg chow/day), melatonin 500 μg/day, melatonin 1000 μg/day, melatonin 500 μg/day+9cRA and melatonin 1000 μg/day+9cRA. Rats treated with the lower dose of melatonin 500 μg+9cRA show the greatest degree of tumor regression (78%), with 54% undergoing complete regression and a significant increase in apoptotic cells observed by TUNEL Assay. Furthermore, tumor multiplicity and burden were significantly decreased by the combination of melatonin and 9cRA.