Home page News Related Researches 2020-2029

IL-1β circuit: A crosstalk interrupted by melatonin

Published on Friday, 17 April 2026

Abstract

Invasion and migration are significant challenges for treatment of oral squamous cell carcinomas (OSCCs). Tumor-associated macrophages (TAMs) interact with cancer cells and are involved in tumor progression.

Our recent study demonstrated that melatonin inhibits OSCC invasion and migration; however, the mechanism by which melatonin influences crosstalk between TAMs and OSCCs is poorly understood.

In this study, a co-culture system was established to explore the interactions between human monocytic cells (THP-1 cells) and human tongue squamous cell carcinoma cells (SCC-15 cells).

The results were verified using monocyte-derived macrophages (MDMs) isolated and differentiated from primary peripheral blood mononuclear cells.

In vivo, assays were performed to confirm the anticancer effects of melatonin. SCC-15 cells co-cultured with THP-1 cells or MDMs exhibited increased migration and invasion, which was reversed by melatonin.

Co-culture also increased the expression of macrophage migration inhibitory factor (MIF), CD40, CD163 and IL-1β, and these changes were also reversed by melatonin.

Moreover, IL-1β secretion in THP-1 cells was MIF- and NLR family pyrin domain-containing 3 (NLRP3)-dependent, and treated with IL-1β enhanced the invasion and migration of SCC-15 cells.

Furthermore, melatonin treatment significantly decreased tumor volumes and weights, and tumors from mice treated with melatonin had lower levels of MIF, NLRP3, and IL-1β than tumor from control mice.

These results demonstrate that macrophages facilitate the progression of OSCCs by promoting the MIF/NLRP3/IL-1β signaling axis, which can be interrupted by melatonin.

Therefore, melatonin could act as an alternative anticancer agent for OSCCs by targeting this signaling axis.

Download the complete article

About this publication.

The Di Bella's Method: Use of Melatonin, Somatostatin/Octreotide analogues and/or derivatives with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Head and Neck Cancer:

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- 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 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);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);