TRANSCRIPTIONAL ANALYSIS OF ZINC-DEPENDENT HISTONE DEACETYLASES IN SEVERAL HUMAN CANCER CELLS
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.17983Keywords:
cancer cell lines, HDAC inhibitors, histone deacetylase, transcriptional profileAbstract
Histone deacetylases, especially zinc-dependent deacetylases HDACs, are among attractive drug targets for treating cancer in recent years. Aim: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.
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