Effects of melatonin on the toxicity and proliferation of human anaplastic thyroid cancer cell line

Published on Friday, 01 October 2021

Abstract

Background: Thyroid carcinoma is the most common endocrine malignancy and anaplastic thyroid carcinoma (ATC) is a rare but most aggressive cancer. Melatonin has enhanced or induced apoptosis in many different cancer cells, however, there has not been any study on the effects of melatonin in the treatment of ATC. In this study, we examined the effect of melatonin on cytotoxicity in the human ATC cell line.

Materials and methods: Cultured ATC cells were treated at melatonin concentrations 0.6, 1, 4, 16, 28 mM for 24 h. The MTT assay was performed to examine cell viability. Cytotoxicity was assayed with the determination of lactic dehydrogenase (LDH) activity. Apoptosis was detected by acridine orange/ethidium bromide and Hoechst 33342 staining. Giemsa staining is considered for evaluating the morphological changes of ATC cells. The reproductive ability of cells to form a colony was evaluated by the clonogenic assay.

Results: Results showed that melatonin could significantly decrease cell viability and the lowest cell viability was observed at 28 mM, 10.26 % ± 0.858 versus control. Similar results were obtained when analyzing LDH activity. The highest LDH levels were observed at 16 and 28 mM (546.08 ± 4.66, 577.82 ± 3.14 munit/mL versus control) that confirmed the occurrence of late apoptosis. The clonogenic assay showed that cells at the high concentration of melatonin (16 and 28 mM) don't enable to form the colony that approved the occurrence of reproductive death.

Conclusion: Our results showed a dose-dependent cytotoxic effect of melatonin on ATC cells that significantly decreased cell viability and induced cell reproductive death at the concentration greater than 1 mM and findings suggested that MLT might be useful as an adjuvant in ATC therapy.

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- 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;

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- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

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- 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);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);