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 TGF beta-1 pathway, leading to increased TGF beta-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-TGF beta-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 TGF beta-1-dependent mechanism, involving down-regulation of both MDM2 and Akt-phosphorylation.

Melatonin and vitamin D-3 synergistically down-regulate Akt and MDM2 leading to TGF beta-1-dependent growth inhibition of breast cancer cells / Proietti, Sara; Cucina, Alessandra; D'Anselmi, Fabrizio; Dinicola, Simona; Alessia, Pasqualato; Elisabetta, Lisi; Bizzarri, Mariano. - In: JOURNAL OF PINEAL RESEARCH. - ISSN 0742-3098. - 50:2(2011), pp. 150-158. [10.1111/j.1600-079x.2010.00824.x]

Melatonin and vitamin D-3 synergistically down-regulate Akt and MDM2 leading to TGF beta-1-dependent growth inhibition of breast cancer cells

PROIETTI, SARA;CUCINA, Alessandra;D'ANSELMI, FABRIZIO;DINICOLA, SIMONA;BIZZARRI, Mariano
2011

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 TGF beta-1 pathway, leading to increased TGF beta-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-TGF beta-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 TGF beta-1-dependent mechanism, involving down-regulation of both MDM2 and Akt-phosphorylation.
2011
melatonin; transforming growth factor beta 1; vitamin d3; akt; mdm2; smad3
01 Pubblicazione su rivista::01a Articolo in rivista
Melatonin and vitamin D-3 synergistically down-regulate Akt and MDM2 leading to TGF beta-1-dependent growth inhibition of breast cancer cells / Proietti, Sara; Cucina, Alessandra; D'Anselmi, Fabrizio; Dinicola, Simona; Alessia, Pasqualato; Elisabetta, Lisi; Bizzarri, Mariano. - In: JOURNAL OF PINEAL RESEARCH. - ISSN 0742-3098. - 50:2(2011), pp. 150-158. [10.1111/j.1600-079x.2010.00824.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/378352
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