机构：[1]Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, China,[2]Department of Basic Medical Science, Xiamen Medical College, Xiamen, China,[3]Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Science, Guangzhou, China,[4]Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China,[5]School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China,[6]The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China,深圳医学信息中心中国医学科学院阜外医院深圳医院[7]Guangzhou Baiyunshan Ming Xing Pharmaceutical Co., Ltd., Guangzhou, China,[8]Department of Pharmacy, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China,深圳大学总医院深圳市康宁医院深圳医学信息中心[9]Department of Breast Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China,大德路总院乳腺科大德路总院乳腺科广东省中医院[10]Shenzhen International Institute for Biomedical Research, Shenzhen, China,[11]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
Triple-negative breast cancer (TNBC) has been acknowledged as an aggressive disease with worst prognosis, which requires endeavor to develop novel therapeutic agents. Bruceae fructus oil (BO), a vegetable oil derived from the fruit of Brucea javanica (L.) Merr., is an approved marketable drug for the treatment of cancer in China for several decades. Despite that the anti-breast cancer activity of several quassinoids derived from B. javanica has been found, it was the first time that the potential of BO against TNBC was revealed. Although BO had no cytotoxicity on TNBC cell lines in vitro, the oral administration of BO exhibited a gut microbiota-dependent tumor suppression without toxicity on the non-targeted organs in vivo. By metagenomics and untargeted metabolomics, it was found that BO not only altered the composition and amino acid metabolism function of gut microbiota but also regulated the host's amino acid profile, which was in accordance with the metabolism alternation in gut microbiota. Moreover, the activity of mTOR in tumor was promoted by BO treatment as indicated by the phosphorylation of 4E-binding protein 1 (4E-BP1) and ribosomal protein S6, and hyper-autophagy was consequently restrained. By contrast, the failure of tumor suppression by BO under pseudo germ-free (PGF) condition came with indistinctive changes in autophagy and mTOR activity, implying the critical role of the gut microbiota in BO's anticancer activity. The present study highlighted a promising application of BO against breast cancer with novel efficacy and safety.</p>
基金：
This work was financially supported by the National Natural
Science Foundation of China (81902709, 81900238, 81974571),
China Postdoctoral Science Foundation funded project
(2018M643300, 2020M682683), Natural Science Foundation of
Guangdong (2018A0303130102, 2019A1515010815), Science
and Technology Bureau of Foshan (FS0AA-KJ218-1301-0008,
FS0AA-KJ819-4901-0082), Foshan Medicine Dengfeng Project of
China (2019–2021), and Science and Technology Planning
Project of Shenzhen City (JCYJ20190808114807611).
第一作者机构：[1]Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, China,
共同第一作者：
通讯作者：
通讯机构：[1]Affiliated Foshan Maternity and Child Healthcare Hospital, Southern Medical University, Foshan, China,[6]The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China,[10]Shenzhen International Institute for Biomedical Research, Shenzhen, China,[11]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Jiyan Su,Xiaohong Chen,Yuanjie Xiao,et al.Bruceae Fructus Oil Inhibits Triple-Negative Breast Cancer by Restraining Autophagy: Dependence on the Gut Microbiota-Mediated Amino Acid Regulation[J].FRONTIERS IN PHARMACOLOGY.2021,12:doi:10.3389/fphar.2021.727082.
APA：
Jiyan Su,Xiaohong Chen,Yuanjie Xiao,Dan Li,Muxia Li...&Chenglai Xia.(2021).Bruceae Fructus Oil Inhibits Triple-Negative Breast Cancer by Restraining Autophagy: Dependence on the Gut Microbiota-Mediated Amino Acid Regulation.FRONTIERS IN PHARMACOLOGY,12,
MLA：
Jiyan Su,et al."Bruceae Fructus Oil Inhibits Triple-Negative Breast Cancer by Restraining Autophagy: Dependence on the Gut Microbiota-Mediated Amino Acid Regulation".FRONTIERS IN PHARMACOLOGY 12.(2021)
