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

Frontiers in Oncology

Yi Ma¹  Guijuan Zhang²  Sha Zhan³  Xianxin Yan³  Fengjie Bie³  Xinyi Ma⁴  Yebei Qiu⁵  Jingyu Cao⁵  Min Ma⁵ 

[1] Department of Cellular Biology, Institute of Biomedicine, National Engineering, Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The National Demonstration Center for Experimental Education of Life Science and Technology, Jinan University, Guangzhou, China;School of Nursing, Jinan University, Guangzhou, China;School of Traditional Chinese Medicine, Jinan University, Guangzhou, China;The First Clinical Medical College, Southern Medical University, Guangzhou, China;The Oncology Department, The First Affiliated Hospital of Jinan University, Guangzhou, China;

关键词: β-boswellic acid;    breast precancerous lesions;    glycolysis;    GLUT1;    AMPK;   

DOI  :  10.3389/fonc.2022.896904

来源: DOAJ

【 摘 要 】

Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. β-Boswellic acid (β-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 β-BA could inhibit breast precancerous lesions in rat disease models. Consistently, β-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 β-BA may interfere with the metabolic pathway. Metabolism-related assays showed that β-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 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 be developed as a promising drug candidate for the prevention of breast precancerous lesions.

【 授权许可】

Unknown