β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation

作者：Bie, Fengjie; Zhang, Guijuan; Yan, Xianxin; Ma, Xinyi; Zhan, Sha; Qiu, Yebei; Cao, Jingyu; Ma, Yi; Ma, Min^*

来源：Frontiers in Oncology, 2022, 12: 896904.

DOI：10.3389/fonc.2022.896904

• beta-boswellic acid
• breast precancerous lesions
• glycolysis
• GLUT1
• AMPK

Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. beta-Boswellic acid (beta-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated that beta-BA could inhibit breast precancerous lesions in rat disease models. Consistently, beta-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that beta-BA may interfere with the metabolic pathway. Metabolism-related assays showed that beta-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of beta-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by beta-BA on MCF-10AT. Taken together, beta-BA could relieve precancerous lesions in vivo and in vitro through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for beta-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions.

• 单位
  1; 南方医科大学