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

Qi Feng; Xiuru Li; Wenjing Sun; Yubo Li; Yu Yuan; Baozhang Guan; Shuai Zhang

doi:10.2147/CMAR.S254853

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

Cancer Manag Res. 2020 Aug 5:12:6921-6934. doi: 10.2147/CMAR.S254853. eCollection 2020.

Authors

Qi Feng¹, Xiuru Li¹, Wenjing Sun¹, Yubo Li², Yu Yuan², Baozhang Guan¹, Shuai Zhang³

Affiliations

¹ The First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou, Guangdong 510632, People's Republic of China.
² Tianjin State Key Laboratory of Modern Chinese Medicine, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People's Republic of China.
³ School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, People's Republic of China.

Abstract

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.

Keywords: 6PGD; Ebselen; cancer; oxidative pentose phosphate pathway.

Grants and funding

This work was supported by grants from the National Nature Science Foundation of China (81902826 and 81672781), the Science and Technology Program of Guangzhou (Grant 201807010003), the Program from the Science and Technology Department of Guangdong Province of China (Grant 2017A030313890). This work was also supported by and the Program of Introducing Talents of Discipline to Universities (111 Project, No. B16021).