Inhibitory effects of pharmacological doses of melatonin on aromatase activity and expression in rat glioma cells

Abstract

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours.

Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells.

Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens.

In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens.

These results are supported by three types of evidence.

Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone.

Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay.

Finally, by (RT)-PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells.

We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression.

By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas.

 

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See also:

- Official Web Site: The Di Bella Method;

- 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 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;

- 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;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- 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;

- Neuroblastoma: Complete objective response to biological treatment;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- 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.