Histone Deacetylase HDAC6 Inhibitor CAY10603 Blocks G1/S of the Cell Cycle and Promotes Senescence of Murine Fibroblasts Transformed with E1A and cHa-ras Oncogenes

Abstract

CAY10603 (CAY) is an effective inhibitor of HDAC6 histone deacetylase involved in α-tubulin deacetylation for murine fibroblasts transformed with E1A and cHa-ras oncogenes. In low concentrations, CAY blocks the cell cycle of the G₁/S phase of these cells and slows down their proliferation, but does not provoke apoptotic death. CAY treatment in combination with sodium butyrate generates accelerated senescence of E1A + cHa-ras-transformants. In murine fibroblasts transformed by oncogenes of E1A and cHa-ras CAY is an efficient inhibitor of histone deacetylase HDAC6 in relation to α-tubulin as its substrate. The G₁/S cell cycle block takes place at low concentrations of CAY in these cells. Their proliferation slows down, but apoptotic death is not provoked. CAY exposure also results in the accumulation of autophagic vacuoles and autophagosome protein LC3 in the cytoplasm of E1A + cHa-ras cells that can manifest participation of HDAC6 in autophagy induction in these transformed cells.