DNMTs inhibitor Procyanidin B2 reactivates PTEN's regulatory effects on abnormal glucose metabolism in gastric cancer
DNMTs inhibitor Procyanidin B2 reactivates PTEN's regulatory effects on abnormal glucose metabolism in gastric cancer
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DOI：
10.1016/j.jff.2024.106053
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发表时间：
2024-02-08
影响因子：
5.6
通讯作者：
Cao，Xueyuan
中科院分区：
文献类型：
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作者：
Cao，Donghui;Jia，Zhifang;Cao，Xueyuan
肿瘤抑制因子PTEN在胃癌（GC）中异常沉默。通过DNA去甲基化激活PTEN是治疗GC的一种潜在策略。原花青素B2 （Procyanidin B2, PB2）是一种有效的DNMT抑制剂，对多种疾病具有积极作用。在我们的研究中，PB2在体外抑制细胞增殖和迁移，诱导细胞凋亡，在体内抑制肿瘤的发生和发展。PB2通过靶向和联合dnmt降低甲基化并重新激活PTEN表达。靶向糖代谢和海马分析表明，PTEN通过hk1介导的G6P和pfk1介导的F1,6-2P抑制细胞增殖，并且PTEN的肿瘤抑制作用不依赖于其磷酸酶活性。此外，PTEN启动子甲基化可以作为预测GC发展的潜在标记。这项工作旨在研究PB2是否通过重新激活PTEN的肿瘤抑制功能来抑制GC，为开发医用和可编辑的天然化合物提供有力的工具。
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 apoptosisin vitro, and inhibited tumorigenesis and developmentin 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.