Pro-GA is a prodrug form of N-glutaryl-L-alanine and an inhibitor of γ-glutamylcyclotransferase (GGCT), an enzyme involved in glutathione metabolism.1 It reduces the viability of RT-112 bladder cancer cells, which have a high expression of GGCT (IC50 = 73.9 ?M), and UM-UC-3 and T24 bladder cancer cells (IC50s = 58.5 and 57 ?M, respectively). It enhances growth inhibition induced by mitomycin C in RT-112 cells. Pro-GA (50, 75, and 100 ?M) also inhibits the proliferation of MCF-7 breast cancer cells.2 It increases the production of reactive oxygen species (ROS) and induces senescence in MCF-7 cells, effects that can be blocked by N-acetylcysteine (NAC). Pro-GA (25 mg/kg) reduces tumor weight in an MCF-7 mouse xenograft model.
References:
[1]. Hanada, E., Kageyama, S., Murai, R., et al.Pro-GA, a novel inhibitor of γ-glutamylcyclotransferase, suppresses human bladder cancer cell growthAnticancer Res.39(4)1893-1898(2019).
[2]. Ii, H., Taniguchi, K., Yoshiya, T., et al.The γ-glutamylcyclotransferase inhibitor Pro-GA induces an antiproliferative effect through the generation of mitochondrial reactive oxygen speciesAnticancer Res.42(9)4311-4317(2022).