The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype.

Abstract

Triple-negative breast cancer (TNBC) is a very aggressive type of tumour and its aggressiveness is linked to E-cadherin downregulation. In estrogen-sensitive breast cancer, high levels of E-cadherin fit with high levels of ERα and MTA3 (a component of the transcription Mi-2/NuRD complex with intrinsic DAC activity). In TNBC the E-cadherin downregulation could be due to epigenetic silencing of the CDH1 gene as well as to the lack of a fully functioning ERα-activated pathway. We report that the pan-histone deacetylase inhibitor LBH589, a potent anti-proliferative agent, induced E-cadherin expression on cell membranes of MDA-MB-231 cells (TNBC), determining a reduction of cell invasion and migration. Even though E-cadherin expression in breast cancer is also regulated by estradiol and the ERα/MTA3/Snail/Slug pathway, LBH589 is able to increase E-cadherin without affecting the estrogen pathway. In fact, no expression of ERα, PR and FoxA1 was observed in MDA-MB-231 cells before and after LBH589 treatment; furthermore, the drug caused an increase in Snail and Slug expression with a concomitant reduction of MTA3 levels. Taking into consideration its anti-proliferative and anti-invasive properties, we suggest the use of LBH589 in aggressive breast cancer refractory to hormonal therapy.

• Authors: Nicoletta Fortunati, Francesca Marano, Andrea Bandino, Roberto Frairia, Maria Graziella Catalano, Giuseppe Boccuzzi
• Journal: International journal of oncology (Int J Oncol) Vol. 44 Issue 3 Pg. 700-8 (Mar 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24366407 (Publication Type: Journal Article)

Chemical References

• Cadherins
• ESR1 protein, human
• Estrogen Receptor alpha
• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Indoles
• Estradiol
• Panobinostat

Topics

• Breast Neoplasms (drug therapy, genetics, pathology)
• Cadherins (biosynthesis)
• Cell Line, Tumor
• Epigenesis, Genetic
• Estradiol
• Estrogen Receptor alpha (biosynthesis)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Histone Deacetylase Inhibitors (administration & dosage)
• Humans
• Hydroxamic Acids (administration & dosage)
• Indoles (administration & dosage)
• Neoplasm Invasiveness (genetics)
• Panobinostat