Figure 2
From: A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth
C1A is a selective inhibitor of HDAC6 associated with a sustained effect. (A) Inhibition of HDAC6 substrates by C1A (1 μ M; 4 h) relative to SAHA in HCT-116 cells. (B) Drug concentration-dependent acetylation of α-tubulin at 4 h, and (C) at 24 h relative to acetyl histone H3 expression. (D) Effect of 10 μ M C1A or SAHA on acetylation of α-tubulin in HCT-116 cells following 4 h drug incubation and washout (cells collected 3 h after washout). (E) Cognate effect of C1A and SAHA and C1A on HSP90 client protein CDK4 following 24 h treatment. The HSP90 inhibitor, 17-AAG, was used as a positive control. (F) Effect of C1A on the growth of DNA repair-deficient and repair-competent cells relative to chlorambucil. UV23 and UV96 cell lines are deficient in XPB and ERCC1, respectively; proteins involved in the nucleotide excision repair pathway. Irs1 and Irs1SF are deficient in XRCC2 and XRCC3, respectively; proteins involved in the homologous recombination repair pathway. XRS5 is deficient in XRCC5; protein involved in the non-homologous end-joining pathway. Growth curves in parental repair-competent cell lines AA8 (for UV23, UV96 and Irs1SF), CHO-K1 (for XRS5) and V79 (for Irs1) are also presented.
