Poorly differentiated and anaplastic thyroid carcinomas are aggressive human cancers that are resistant to conventional therapy. DAC inhibitors (DACi) are a promising class of drugs, acting as anti-proliferative agents by inducing apoptosis and cell cycle arrest.
Panobinostat (LBH589) is a potent DACi belonging to a structurally novel cinnamic hydroxamic acid class of compounds, able to inhibit the activity of different isoforms of HDACs (HDAC 1, 36) and the proliferation of tumour cells at nanomolar concentration.
Aim of the present work was to evaluate the effect of panobinostat on the growth of poorly differentiated and anaplastic thyroid cancer cell lines. Cells were treated with increasing doses of panobinostat (05102550100200500 nM) up to 72 h. After treatment, we evaluated: (1) cell viability and cytotoxicity by WST-1 method; (2) cell cycle progression by FACS analysis. Our data demonstrate that panobinostat has cytotoxic effects on both poorly differentiated and anaplastic thyroid cancer cell lines, and this is through G2 cell cycle arrest and apoptosis induction. Moreover, panobinostat is able to induce acetylation of histones and tubulin in both types of cell lines, as demonstrated by western blot analysis. These data suggest a mechanistic link between histone and tubulin acetylation, and the panobinostat-induced cytotoxic effects. This study supports the rationale for further clinical development of panobinostat as a potential therapy for the treatment of poorly differentiated and anaplastic thyroid cancers.
03 - 07 May 2008
European Society of Endocrinology