In this in vivo study, we evaluated the melatonin antitumor activity using an alternative noninvasive delivery route against prostate tumor cells (LNCaP) xenografted into nude mice and, subsequently, we tried to shed light on the melatonin mechanism(s) of action by looking at the posttranslational regulation of SIRT1. The gene discussed is SIRT1; the disease is prostate neoplasm.