TRANSCRIPTIONAL ANALYSIS OF ZINC-DEPENDENT HISTONE DEACETYLASES IN SEVERAL HUMAN CANCER CELLS

Histone deacetylases, especially zinc-dependent deacetylases HDACs, are among attractive drug targets for treating cancer in recent years.

To explore the expression level of HDACs in several human cancer cell lines and examine the possible association between their expression and the sensitivity/resistance to the selective- or pan-HDAC inhibitors.

The RNA expression of 11 HDACs isoforms was assayed in HeLa, HepG2, AV3, HEK293, A549, and K562 cells by semiquantitative reverse transcription-polymerase chain reaction. The sensitivity/resistance of these cell lines to the pan- or selective- HDAC inhibitors was estimated by MTS assay.

The relative transcription of HDACs genes demonstrated that members of Class I HDAC (HDAC1, 2 and 3) and members of Class II HDAC (HDAC4, 5, 6 and 7) had slight to significant levels of expression in cell lines under study with no dominant HDAC-subtype gene transcription. pan-HDAC inhibitor demonstrated superior antitumor activity compared to HDAC isoform-selective inhibitor.

The absence of the dominant HDAC-subtype gene transcription in different human cancer cell lines explains the inferior efficacy of HDAC isoform-selective inhibitors as compared to pan-HDAC inhibitors.