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Melatonin-induced KiSS1 expression inhibits triple-negative breast cancer cell invasiveness

Published on Friday, 17 March 2023

Abstract

Breast cancer is one of the most common types of cancer in women, and its metastasis increases the risk of mortality. Melatonin, a hormone that regulates the circadian rhythm, has been revealed to inhibit breast cancer growth and metastasis. However, its involvement in highly metastatic triple-negative breast cancer cells is yet to be elucidated.

The present study demonstrated that melatonin inhibited the metastatic abilities of triple-negative breast cancer cells and prolonged its inhibitory effect via the expression of kisspeptin (KiSS1), which is a suppressor of metastasis.

Melatonin at concentrations ranging from 1 nM to 10 µM did not affect the proliferation of metastatic MDA-MB-231 and HCC-70 triple-negative breast cancer cells.

However, melatonin repressed invasiveness in triple-negative breast cancer cells.

Additionally, conditional medium from melatonin-treated MDA-MB-231 cells repressed the invasiveness of triple-negative breast cancer cells. Melatonin promoted the production of KiSS1, a metastasis suppressor encoded by the KiSS1 gene.

In addition, melatonin increased KiSS1 expression via the expression and transcriptional activation of GATA binding protein 3. Silencing of KiSS1 weakened melatonin inhibition of breast cancer cell invasiveness.

Therefore, the present study concluded that melatonin activates KiSS1 production in metastatic breast cancer cells, suggesting that melatonin activation of KiSS1 production may regulate the process of breast cancer metastasis.

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About this publication.

- 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: Melmethoatonin 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 - 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);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);