Adapalene inhibits ovarian cancer ES-2 cells growth by targeting glutamic-oxaloacetic transaminase 1.Bioorg Chem 2019; 93:103315BC
Glutamic-oxaloacetic transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements for sustained proliferation. As such, the GOT1 inhibitor may provide a new strategy for the treatment of various cancers. Adapalene has been approved by FDA for the treatment of acne, pimples and pustules, and it may also contribute to the adjunctive therapy for advanced stages of liver and colorectal cancers. In this work, we first examined the enzyme inhibition of over 500 compounds against GOT1 in vitro. As a result, Adapalene effectively inhibited GOT1 enzyme in a non-competitive manner. MST and DARTS assay further confirmed the high affinity between Adapalene and GOT1. Furthermore, the growth and migration of ovarian cancer ES-2 cells were obviously inhibited by the treatment of Adapalene. And it induced the apoptosis of ES-2 cells according to Western blot and Hoechst 33258 straining. In addition, molecular docking demonstrated that Adapalene coordinated in an allosteric site of GOT1 with low binding energy. Furthermore, knockdown of GOT1 in ES-2 cells decreased their anti-proliferative sensitivity to Adapalene. Together, our data strongly suggest Adapalene, as a GOT1 inhibitor, could be regarded as a potential drug candidate for ovarian cancer therapy.