Fig. 2: Inhibition of HDAC1/2/3 attenuates TMZ-induced DDR activation and increases TMZ-induced DSBs by impairing HR-mediated repair. | Cell Death & Disease

Fig. 2: Inhibition of HDAC1/2/3 attenuates TMZ-induced DDR activation and increases TMZ-induced DSBs by impairing HR-mediated repair.

From: Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression

Fig. 2

A Effect of MS-275 on the TMZ-induced activation of the DDR kinase ATM and its targets CHK1, CHK2, p53 determined by western blot analysis. LN229 and A172 cells were exposed to indicated drugs. ß-ACTIN and TALIN served as loading controls. B MS-275 increases TMZ-induced DSB formation. LN229 and A172 cells were exposed to indicated drugs and DSBs were detected by neutral comet assay. Cells exposed to t-BuOOH served as a positive control. Indicated significances result from an unpaired t-test with Welch’s correction. C Effect of MS-275 on HR activity was determined in LN229 DRGFP clones c. 46, c.48, c.47, c.54, and c.62. Flow cytometric analysis was performed 96 h after transient transfection with a SceI expressing plasmid. Indicated significances result from a paired t-test. *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001 and ****P ≤ 0.0001. For A and B cells were exposed to MS-275 (1.5 µM), TMZ (50 µM) and TMZ/MS-275 and assays were performed 72 h later.

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