Here, we report that melatonin delivered by cryopass laser acts as a novel SIRT1 inhibitor and imparts anti-proliferative effects, as demonstrated by the decrease in the nuclear marker for cell proliferation Ki67, in prostate tumor xenografted in mice via inhibiting SIRT1, which in turn acts on ECM, PGC-1α/PPAR-γ pathway and modulates NF-κB signaling. Here, PPARG is linked to prostate neoplasm.