DNMTs inhibitor Procyanidin B2 reactivates PTEN's regulatory effects on abnormal glucose metabolism in gastric cancer

Donghui Cao, Zhifang Jia, Yanhua Wu, Tongrong Su, Yingli Fu, Yingnan Cui, Yuanlin Sun, Yuzheng Zhang, Dongming Li, Yangyu Zhang, Tetsuya Tsukamoto, Jing Jiang, Xueyuan Cao

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor suppressor PTEN was aberrant silenced in gastric cancer (GC) in our previous study. Activation of PTEN through DNA demethylation is a potential strategy for the treatment of GC. Procyanidin B2 (PB2), an effective DNMT inhibitor, exert positive effects on various diseases. In our work, PB2 suppressed cell proliferation and migration while inducing cell apoptosis in vitro, and inhibited tumorigenesis and development in vivo. PB2 hypomethylated and reactivated PTEN expression via targeting and combining with DNMTs. Targeted glucose metabolism and Seahorse analysis showed that PTEN inhibited cell proliferation via HK1-mediated G6P and PFK1-mediated F1,6-2P, and the tumor-suppressor role of PTEN was not dependent on its phosphatase activity. Furthermore, PTEN promoter methylation could be used as a potential marker to predict GC development. This work aimed to investigate whether PB2 inhibit GC by reactivating PTEN's tumor suppressor function, providing a powerful tool in the development of medical and editable natural compounds.

Original languageEnglish
Article number106053
JournalJournal of Functional Foods
Volume114
DOIs
Publication statusPublished - 03-2024

All Science Journal Classification (ASJC) codes

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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