Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft

SIMPLE SUMMARY: The likelihood of prostate tumor diagnosis in men increases with age, raising the need for novel therapies to better treat this disease. This research examined mechanisms on the basis of the anti-tumor effects of melatonin against prostate tumor cells xenografted into nude mice when delivered by a new and alternative route based on transdermal administration by cryopass-laser treatment. Despite other signaling pathways targeted by this molecule that have already been described, here we demonstrate that the significant anti-proliferative effect displayed by transdermal melatonin is also due to the Sirtuin1 pathway modulation. ABSTRACT: Melatonin displays antitumor activity in several types of malignancies; however, the best delivery route and the underlying mechanisms are still unclear. Alternative non-invasive delivery route based on transdermal administration of melatonin by cryopass-laser treatment demonstrated efficiency in reducing the progression of LNCaP prostate tumor cells xenografted into nude mice by impairing the biochemical pathways affecting redox balance. Here, we investigated the impact of transdermal melatonin on the tumor dimension, microenvironment structure, and SIRT1-modulated pathways. Two groups (vehicle cryopass-laser and melatonin cryopass-laser) were treated for 6 weeks (3 treatments per week), and the tumors collected were analyzed for hematoxylin eosin staining, sirius red, and SIRT1 modulated proteins such as PGC-1α, PPARγ, and NFkB. Melatonin in addition to simple laser treatment was able to boost the antitumor cancer activity impairing the tumor microenvironment, increasing the collagen structure around the tumor, and modulating the altered SIRT1 pathways. Transdermal application is effective, safe, and feasible in humans as well, and the significance of these findings necessitates further studies on the antitumor mechanisms exerted by melatonin.