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

Cancers · 5 authors, 6 centres

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TL;DR

This preclinical study used a mouse xenograft model to test transdermal melatonin delivery via cryopass-laser. It found that this treatment modulated the SIRT1 pathway, increased tumor collagen content, and reduced markers of proliferation and neovascularization.

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This preclinical study investigated the effects of transdermal melatonin administered via cryopass-laser on LNCaP prostate tumor cells xenografted into nude mice. Two groups were treated for 6 weeks. Tumor analysis included histology and assessment of SIRT1-modulated proteins. Results indicated that melatonin treatment modulated SIRT1 expression, which influenced the PGC-1α/PPARγ pathway and NF-κB signaling. It also increased total and type III collagen around tumors, while reducing proliferation markers like ki-67 and neovascularization. Limitations include the use of a single cell line and the absence of protein-level validation via Western Blot or ELISA. The findings suggest a multi-faceted antitumor mechanism but require further study to confirm direct effects in humans.

STUDY TYPE

other

SPECIALTY

oncology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10605886

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

Cancers

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ABSTRACT

Abstract 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. Keywords: melatonin, oxidative stress, tumor, sirtuin1, proliferator-activated receptor gamma, PPAR-gamma coactivator 1-alpha, nuclear factor kappa B

CITATION EXPORT

Francesca Bonomini, Gaia Favero, Anna Petroni et al.. Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor Xenograft. Cancers. (2023). https://doi.org/10.3390/cancers15204908

AUTHORS

5 · 6 CENTRES

Francesca Bonomini, Gaia Favero, Anna Petroni, Rita Paroni, Rita Rezzani

1Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy; [email protected] (F.B.); [email protected] (G.F.)
2Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs (ARTO)”, University of Brescia, 25123 Brescia, Italy
3Italian Society for the Study of Orofacial Pain (Società Italiana Studio Dolore Orofacciale—SISDO), 25123 Brescia, Italy
4Biomedicine and Nutrition Research Network, Via Paracelso 1, 20129 Milan, Italy; [email protected]
5Department of Medicine, Surgery and Neuroscience, University of Siena, 53100 Siena, Italy
6Clinical Biochemistry and Mass Spectrometry, Department of Health Sciences, San Paolo Hospital, Università degli Studi di Milano, 20142 Milan, Italy; [email protected]