Auhtors: Proietti S, Cucina A, D’Anselmi F, Dinicola S, Pasqualato A, Lisi E, Bizzarri M
PMID: 21091766 DOI: 10.1111/j.1600-079X.2010.00824.x
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, involving down-regulation of both MDM2 and Akt-phosphorylation.
Keywords: melatonin, vitamin d3, breast cancer, cancer cells
Source: https://pubmed.ncbi.nlm.nih.gov/21091766/
Archive: https://archive.is/1kFPS
