Melatonin inhibits growth of B16 melanoma in C57BL/6 mice

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Published on Friday, 16 October 2020

Abstract

Melatonin (N-acetyl-5-methoxytryptamine) has oncostatic properties in a wide variety of tumors.

In melanoma, melatonin displayed growth suppressive effects in cultured cell lines and tumors. Thus far, however, there is no evidence of orally administrated melatonin reducing melanoma tumor growth. Therefore, the current study investigated the preventive effect of melatonin on C57BL/6 mice injected with B16-F10 murine metastatic melanoma cells.

The animals were divided into two groups; control (vehicle) and melatonin pre-treated with oral melatonin in the drinking water (10 mg/kg/day) for 15 days.

Grossly, the control animals had a significant exponential increase in tumor size until day 33, and all control animals were dead by day 38; conversely, melatonin pre-treated mice demonstrated delayed tumour appearance as well as decreased tumour volume and increased survival rates.

PCNA immunostaining corroborated these data and demonstrated a significant reduction in the number of proliferating cells in the melatonin-treated mice (P < 0.005).

Interestingly, histopathological analysis revealed the presence of undifferentiated and pleomorphic cells associated with higher mitotic rate in the control group, while epithelioid-shaped cells, sometimes containing melanin were clearly identified in melatonin-treated animals.

Mitochondrial parameters measurement showed greater PTP opening and increased mitochondrial nitrite level associated in melatonin-pretreated animals.

Finally, the decreased P-ERK1,2 cytoplasmic expression in melatonin mice compared with the controls supports the conclusion that the MAPK signalling pathway is repressed by melatonin in B16-F10 melanoma.

Collectively, these results suggest for the first time that orally-administered melatonin reduces malignant melanoma progression in vivo and increases the percent of survival by lowering tumor cells proliferation due to mitochondrial dependent cytotoxicity and decreased P-ERK1,2 expression.

This study demonstrates the chemopreventive potential of melatonin against malignant melanoma in C57BL/6 mice.

NOTE: This publication cites (Ref. N.47): Di Bella G., Mascia F., Gualano L., Di Bella L. - Melatonin anticancer effect: review. Int J Mol Sci. 2013;14:2410–2430.

 

About this publication.

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;

- 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 - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - 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 - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);


 


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- 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;

- 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;

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