Home page News Related Researches 2010-2019

Melatonin: an inhibitor of breast cancer

Published on Tuesday, 21 April 2015

Abstract

This review discusses recent work on melatonin-mediated circadian regulation and molecular and metabolic signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN).

Anti-proliferative effects of the circadian melatonin signal are, typically, mediated through mechanisms involving the activation of MT1 melatonin receptors expressed in human breast cancer cell lines and xenografts.

In estrogen receptor alpha (ERα)-positive human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα. Melatonin also regulates the transcriptional activity of additional members of the nuclear receptor super-family, enzymes involved in estrogen metabolism, and the expression of core clock and clock-related genes.

Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance.

Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition.

Studies demonstrate that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in both rats and humans indicate that LEN induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, signaling, and drives breast tumors to endocrine and chemotherapeutic resistance.

These data provide the strongest mechanistic support yet for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LEN.

Download the complete article

About this publication.

The Di Bella's Method: Use of Melatonin (together with others chemical compounds) in Breast Cancer:

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day 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 - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- 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 - Calcium, 2 grams per day, orally);