Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells.

Inhibition of G9a by a small molecule inhibitor, UNC0642, induces apoptosis of human bladder cancer cells. Acta Pharmacol Sin. 2019 Feb 14;: Authors: Cao YP, Sun JY, Li MQ, Dong Y, Zhang YH, Yan J, Huang RM, Yan X Abstract Urinary bladder cancer (UBC) is characterized by frequent recurrence and metastasis despite the standard chemotherapy with gemcitabine and cisplatin combination. Histone modifiers are often dysregulated in cancer development, thus they can serve as an excellent drug targets for cancer therapy. Here, we investigated whether G9a, one of the histone H3 methyltransferases, was associated with UBC development. We first analyzed clinical data from public databases and found that G9a was significantly overexpressed in UBC patients. The TCGA Provisional dataset showed that the average expression level of G9a in primary UBC samples (n = 408) was 1.6-fold as much as that in normal bladder samples (n = 19; P < 0.001). Then we used small interfering RNA to knockdown G9a in human UBC T24 and J82 cell lines in vitro, and observed that the cell viability was significantly decreased and cell apoptosis induced. Next, we choosed UNC0642, a small molecule inhibitor targeting G9a, with low cytotoxicity, and excellent in vivo pharmacokinetic properties, to test its anticancer effects against UBC cells in vitro and in vivo. Treatment with UNC0642 dose-dependently decreased the viability of T24, J82, and 5637 cells with th...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research