Discovery of Ebselen as an Inhibitor of 6PGD for Suppressing Tumor Growth

INTRODUCTION: The 6-phosphogluconate dehydrogenase (6PGD) was upregulated in many solid cancers and plays an important role in tumorigenesis. In the present study, we want to discover an old drug as an inhibitor of 6PGD for suppressing tumor growth. METHODS: We determined the expression of 6PGD in cancer tissues using Gene Expression Omnibus (GEO) profiles and explored the importance of 6PGD expression in cancer progression by using Kaplan–Meier Plotter. We identified Ebselen as a 6PGD inhibitor by using 6PGD in vitro enzyme activity assay. Cell viability, cell proliferation, tumor growth and cell metabolism assay were used to explore the role of 6PGD and its inhibitor in cancer cells. RESULTS: We found that the expression of 6PGD was upregulated in different cancer tissues and it can promote tumorigenesis. Here, we analyzed our 6PGD inhibitor screening data again and found an old drug Ebselen, which blocks cancer cell proliferation and tumor growth by inhibiting 6PGD enzyme activity, while knocking down 6PGD would partially abolish the inhibition of Ebselen on cell proliferation and cell metabolism. CONCLUSION: Our results suggested that the conventional drug Ebselen could serve as a novel inhibitor of 6PGD for suppressing cancer growth by inhibiting 6PGD enzyme activity.