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Updated: Jul 12, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Melatonin Modulates the SIRT1-Related Pathways via Transdermal Cryopass-Laser Administration in Prostate Tumor
Francesca Bonomini1,2,3, Gaia Favero1,2, Anna Petroni4,5
1Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy.
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.
Insights
Transdermal melatonin delivery via cryopass-laser treatment effectively reduced prostate tumor growth in mice. This approach enhanced the tumor microenvironment and modulated key pathways, suggesting potential for human cancer therapy.
Area of Science:
- Oncology
- Biochemistry
- Dermatology
Background:
- Melatonin exhibits antitumor properties across various cancers.
- Optimal delivery routes and mechanisms for melatonin's anticancer effects remain under investigation.
- Non-invasive transdermal delivery presents a promising alternative for melatonin administration.
Purpose of the Study:
- To investigate the impact of transdermal melatonin delivered via cryopass-laser treatment on prostate tumor progression.
- To analyze alterations in tumor microenvironment structure and SIRT1-modulated pathways.
- To evaluate the efficacy and feasibility of this novel transdermal melatonin delivery method.
Main Methods:
- LNCaP prostate tumor xenografts in nude mice were treated with either vehicle or melatonin via cryopass-laser for 6 weeks.
- Tumor tissues were analyzed using hematoxylin eosin and sirius red staining.
- Expression of SIRT1-modulated proteins including PGC-1α, PPARγ, and NFkB was assessed.
Main Results:
- Transdermal melatonin significantly impaired tumor progression by affecting redox balance pathways.
- The treatment enhanced antitumor activity by modifying the tumor microenvironment.
- Increased collagen structure and modulation of SIRT1 pathways were observed around the tumor.
Conclusions:
- Transdermal melatonin delivery using cryopass-laser treatment demonstrates significant antitumor efficacy against prostate cancer xenografts.
- This method improves the tumor microenvironment and modulates critical cellular pathways.
- The transdermal approach is safe, feasible in humans, and warrants further investigation for cancer treatment.
