Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells

Yinhua Zhu; Ying Zhang; Qianyu Zhang; Ang Ma; Ying Zhang; Chen Wang; Peng Gao; Qiuyan Guo; Fei Xia; Huan Tang; Chengchao Xu; Jigang Wang

doi:10.1039/D2CC03069A

Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells†

Yinhua Zhu,‡^a Ying Zhang,‡^a Qianyu Zhang,^b Ang Ma,^a Ying Zhang,^a Chen Wang,^a Peng Gao,^a Qiuyan Guo,^a Fei Xia,^a Huan Tang,*^a Chengchao Xu*^a and Jigang Wang

*^a

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* Corresponding authors

^a Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China

^b Pharmaceutical College, Henan University, Kaifeng, 475004, China
E-mail: htang@icmm.ac.cn, ccxu@icmm.ac.cn, jgwang@icmm.ac.cn

Abstract

Whether or not the anticancer activity of gambogic acid is achieved via regulating the cellular metabolic process remains unclear. Here we report that gambogic acid suppresses the pentose phosphate pathway (PPP) by covalently inhibiting the 6-phosphogluconate dehydrogenase (6PGD) protein. This study elucidates the mechanism of action of gambogic acid from the perspective of metabolic reprogramming regulation in cancer cells.

Chemical Communications

Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells†

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Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells

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