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mTOR signaling

Published on Monday, 20 April 2026

Abstract

Hypertrophic scar (HS) is a fibrotic skin condition and characterized by abnormal proliferation of myofibroblasts and accumulation of extracellular matrix. Melatonin, an endogenous hormone, can alleviate fibrosis in multiple models of diseases.

This study examined the effect of melatonin on fibrosis in primary fibroblasts from human HS (HSFs) and a rabbit ear model and potential mechanisms.

Melatonin treatment significantly decreased the migration and contraction capacity, collagen and α-smooth muscle actin (α-SMA) production in HSFs. RNA-sequencing and bioinformatic analyses indicated that melatonin modulated the expression of genes involved in autophagy and oxidative stress.

Mechanistically, melatonin treatment attenuated the AKT/mTOR activation through affecting the binding of MT2 receptor with PI3K to enhance autophagy, decreasing fibrogenic factor production in HSFs.

Moreover, melatonin treatment inhibited HS formation in rabbit ears by enhancing autophagy. The anti-fibrotic effects of melatonin were abrogated by treatment with an autophagy inhibitor (3-methyladenine, 3-MA), an Akt activator (SC79), or an MT2 selective antagonist (4-phenyl-2propionamidotetralin, 4-P-PDOT).

Therefore, melatonin may be a potential drug for prevention and treatment of HS.

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- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day and more orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);