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Molecular and Cellular Mechanisms of Melatonin in Osteosarcoma

Published on Wednesday, 18 December 2019

Abstract

Osteosarcoma, the most common primary bone malignancy, occurs most frequently in adolescents with a peak of incidence at 11-15 years.

Melatonin, an indole amine hormone, shows a wide range of anticancer activities. The decrease in melatonin levels simultaneously concurs with the increase in bone growth and the peak age distribution of osteosarcoma during puberty, so melatonin has been utilized as an adjunct to chemotherapy to improve the quality of life and clinical outcomes.

While a large amount of research has been conducted to understand the complex pleiotropic functions and the molecular and cellular actions elicited by melatonin in various types of cancers, a few review reports have focused on osteosarcoma.

Herein, we summarized the anti-osteosarcoma effects of melatonin and its underlying molecular mechanisms to illustrate the known significance of melatonin in osteosarcoma and to address cellular signaling pathways of melatonin in vitro and in animal models. Even in the same kind of osteosarcoma, melatonin has been sparingly investigated to counteract tumor growth, apoptosis, and metastasis through different mechanisms, depending on different cell lines.

We highlighted the underlying mechanism of anti-osteosarcoma properties evoked by melatonin, including antioxidant activity, anti-proliferation, induction of apoptosis, and the inhibition of invasion and metastasis.

Moreover, we discussed the drug synergy effects of the role of melatonin involved and the method to fortify the anti-cancer effects on osteosarcoma.

As a potential therapeutic agent, melatonin is safe for children and adolescents and is a promising candidate for an adjuvant by reinforcing the therapeutic effects and abolishing the unwanted consequences of chemotherapies.

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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: 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 - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - 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 - 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);