The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)

N. Fortunati (1) , M. G. Catalano (2) , F. Marano (1) , V. Mugoni (1) , M. Pugliese (2) , O. Bosco (2) , F. Mainini (3) , G. Boccuzzi (1, 2)

1 Oncological Endocrinology
2 Department of Clinical Pathophysiology
3 Novartis Farma S.p.A

New drugs with anti-tumor activity, also able to modify the expression of selected molecules, are under evaluation in breast cancer which is becoming resistant to conventional treatment, or in metastatic disease. The sodium-iodide symporter (NIS), which mediates iodide uptake into thyroid cells, and is the molecular basis of radioiodine imaging and therapy in thyroid cancer, is also expressed in a large portion of breast tumors. Since NIS expression in breast cancer is not sufficient for a significant iodide uptake, drugs able to induce its expression and correct function are under evaluation. In the present study, we report for the first time that the pan-deacetylase (DAC) inhibitor LBH589 (panobinostat) significantly induced NIS, both as mRNA and as protein, through the increase of NIS promoter activity, with the final consequence of obtaining a significant up-take of iodide in MCF7, T47D, and MDA-MB231 breast cancer cells. Moreover, we observed that LBH589 causes a significant reduction in cell viability of estrogen-sensitive and -insensitive breast cancer cells within nanomolar range. The anti-tumor effect of LBH589 is sustained by apoptosis induction and cell cycle arrest in G/M. In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease.

Mots clés: DAC inhibitors; Breast cancer; NIS; Targeted therapy; Epigenetic

N. Fortunati, M. G. Catalano, F. Marano, V. Mugoni, M. Pugliese, et al.. The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS). Breast Cancer Research and Treatment, 2010, pp.667-675. ⟨10.1007/s10549-010-0789-z⟩. ⟨hal-00534548⟩