AUTHOR=Bie Fengjie , Zhang Guijuan , Yan Xianxin , Ma Xinyi , Zhan Sha , Qiu Yebei , Cao Jingyu , Ma Yi , Ma Min 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.896904

DOI=10.3389/fonc.2022.896904

ISSN=2234-943X

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