机构:[1]School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China[2]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China广东省中医院[3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China广东省中医院[4]Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China深圳市中医院深圳医学信息中心[5]School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
Emerging evidence has suggested that targeting glycolysis may be a promising strategy for cancer treatment. Betulinic acid (BA) is a natural pentacyclic terpene that has been reported to be active in inhibiting various malignancies. Here, we showed that BA could inhibit aerobic glycolysis activity in breast cancer cell lines MCF-7 and MDA-MB-231 by hampering lactate production, glucose uptake and extracellular acidification rate (ECAR), as well as suppressing aerobic glycolysis-related proteins including c-Myc, lactate dehydrogenase A (LDH-A) and p-PDK1/PDK1 (pyruvate dehydrogenase kinase 1). Mechanistic studies validated Caveolin-1 (Cav-1) as one of key targets of BA in suppressing aerobic glycolysis, as BA administration resulted in Cav-1 upregulation, whereas silencing Cav-1 abrogated the inhibitory effect of BA on aerobic glycolysis. Further investigations demonstrated that BA suppressed aerobic glycolysis in breast cancer cells by regulating the Cav-1/NF-kappa B/c-Myc pathway. More meaningfully, BA significantly inhibited breast cancer growth and glycolytic activity in both the transgenic MMTV-PyVT+/- breast cancer spontaneous model and the zebrafish breast cancer xenotransplantation model without any detectable side effects in vivo. Taken together, our study sheds novel insights into BA as a promising candidate drug for suppressing aerobic glycolysis, highlighting Cav-1 as a potential molecular target of BA and aerobic glycolysis regulation.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81703749, 81703764, 81573651, 81873306]; Guangdong Science and Technology Department [2016A030306025]; Guangzhou Science, Technology and Innovation Commission [805296345055]; Pearl River S&T Nova Program of Guangzhou [201506010098]; Guangdong Provincial Science and Technology Agency; Guangdong Provincial Academy of Traditional Chinese Medicine [2014A020221047]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2016A030313855]; Guangdong High-level University Construction Project [A1-AFD018161Z1510, A1-AFD018171Z11102, A1-AFD018171Z11101]; Guangdong High-level Personnel of Special Support Program [A1-3002-16-111-003]; Guangdong Traditional Chinese Medicine Bureau Project [20181132, 20182044]; Postdoctoral Science Foundation of ChinaChina Postdoctoral Science Foundation [2017 M612644, 2018 T110861, 2017 M622669]; PhD Start-up Fund of Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2017A030310213]; Guangdong Provincial Key Project [2016kzdxm032]; Science and Technology Planning Project of Guangdong Province [2017B030314166]; Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine [YN2018MJ07, YN2018QJ08]
第一作者机构:[1]School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China[2]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
共同第一作者:
通讯作者:
通讯机构:[2]Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[3]Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China[4]Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
推荐引用方式(GB/T 7714):
Jiao Lin,Wang Shengqi,Zheng Yifeng,et al.Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway[J].BIOCHEMICAL PHARMACOLOGY.2019,161:149-162.doi:10.1016/j.bcp.2019.01.016.
APA:
Jiao, Lin,Wang, Shengqi,Zheng, Yifeng,Wang, Neng,Yang, Bowen...&Wang, Zhiyu.(2019).Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway.BIOCHEMICAL PHARMACOLOGY,161,
MLA:
Jiao, Lin,et al."Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway".BIOCHEMICAL PHARMACOLOGY 161.(2019):149-162