Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line
Abstract
AIM: To determine the receptor subtypes of melatonin in estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity.
METHODS: To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERalpha-receptors mRNA was compared with RT-PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin.
RESULTS: Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERalpha mRNA expression was attenuated at melatonin level of 1 x 10(-9) M. Chemosensitivity test revealed that melatonin enhanced anti-tumor effects of paclitaxel among anticancer drugs tested.
CONCLUSION: Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERalpha expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.
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);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- 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);
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- 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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