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Abstract Title:

Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to TGFβ-1-dependent growth inhibition of breast cancer cells.

Abstract Source:

J Pineal Res. 2011 Mar;50(2):150-8. Epub 2010 Nov 22. PMID: 21091766

Abstract Author(s):

Sara Proietti, Alessandra Cucina, Fabrizio D'Anselmi, Simona Dinicola, Alessia Pasqualato, Elisabetta Lisi, Mariano Bizzarri

Article Affiliation:

Department of Experimental Medicine, University La Sapienza, Roma, Italy.

Abstract:

Melatonin and vitamin D3 inhibit breast cancer cell growth and induce apoptosis, but they have never been combined as a breast cancer treatment. Therefore, we investigated whether their association could lead to an enhanced anticancer activity. In MCF-7 breast cancer cells, melatonin together with vitamin D3, induced a synergistic proliferative inhibition, with an almost complete cell growth arrest at 144 hr. Cell growth blockade is associated to an activation of the TGFβ-1 pathway, leading to increased TGFβ-1, Smad4 and phosphorylated-Smad3 levels. Concomitantly, melatonin and D3, alone or in combination, caused a significant reduction in Akt phosphorylation and MDM2 values, with a consequent increase of p53/MDM2 ratio. These effects were completely suppressed by adding a monoclonal anti-TGFβ-1 antibody to the culture medium. Taken together, these results indicate that cytostatic effects triggered by melatonin and D3 are likely related to a complex TGFβ-1-dependent mechanism, involvingdown-regulation of both MDM2 and Akt-phosphorylation.

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Sayer Ji
Founder of GreenMedInfo.com

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