Abstract
The inhibition of the aromatase-induced intratumoral estrogen synthesis is one of the main anticancer pharmacological strategies. The aim of this paper was to study if a melatonin pretreatment prior to aminoglutethimide increases the efficiency of the aromatase inhibitor used in treating breast cancer.
Aminoglutethimide (100 microM) and melatonin (1 nM) significantly decreased cellular aromatase activity in unpretreated MCF-7 cells. A sequential regimen of melatonin (1 nM) followed 24 h later by aminoglutethimide (100 microM) induced a significantly higher decrease in MCF-7 cell aromatase activity to below the values obtained in unpretreated cells.
Melatonin treatment inhibited aromatase mRNA expression in unpretreated cells and a sequential treatment of cells with melatonin followed by aminoglutethimide induced a significant inhibition in the aromatase mRNA expression as compared to cells exposed to the same doses of aminoglutethimide, but without melatonin pretreatment.
The present study demonstrates that a treatment with melatonin followed by aminoglutethimide is the most effective way of reducing the aromatase activity in the MCF-7 cell line. The aminoglutethimide inhibitory effect is more potent when MCF-7 cells are pre-exposed to melatonin.
Our results suggest that melatonin pretreatment increases the reduction of the aromatase activity of cells exposed to aminoglutethimide as a result of the decrease in the aromatase mRNA expression.
The findings presented here point to melatonin pretreatment as a novel and interesting means to increase the efficacy of competitive aromatase inhibitors used in treating breast cancer.
See also:
- Official Web Site: The Di Bella Method;
- 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);
- 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, 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);
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