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3-Bromopyruvic acid regulates glucose metabolism by targeting the c-Myc/TXNIP axis and induces mitochondria-mediated apoptosis in TNBC cells.
| Content Provider | Europe PMC |
|---|---|
| Author | Li, Jiachen Pan, Jianmin Liu, Yang Luo, Xiaohui Yang, Cheng Xiao, Wangfa Li, Qishang Yang, Lihui Zhang, Xiaodong |
| Copyright Year | 2020 |
| Abstract | Aerobic glycolysis is commonly observed in tumor cells, including triple-negative breast cancer (TNBC) cells, and the rate of aerobic glycolysis is higher in TNBC cells than in non-TNBC cells. Hexokinase 2 (HK2) is a key enzyme in the glycolytic pathway and a target of the transcription factor c-Myc, which is highly expressed in TNBC and promotes aerobic glycolysis by enhancing HK2 expression. As an inhibitor of HK2, 3-bromopyruvic acid (3-BrPA) exhibits good therapeutic efficacy in intrahepatic and extrahepatic tumors and inhibits the proliferation of human tumor cells with high expression levels of c-Myc in vivo and in vitro. In addition, 3-BrPA combines with photodynamic therapy to inhibit TNBC cell migration. Thioredoxin-interacting protein (TXNIP) competes with c-Myc to reduce glucose consumption in tumor cells to restrain cell proliferation. A comparative analysis was performed in the present study in TNBC (HCC1143) and non-TNBC (MCF-7) cell lines to explore the effect of 3-BrPA on energy metabolism in TNBC cells and to investigate the possible mechanism of action. Cell viability and apoptosis were detected through Cell Counting Kit-8 and flow cytometry assays, respectively. Expression levels of HK2, glucose transporter 1, TXNIP, c-Myc and mitochondria-regulated apoptosis pathway proteins were measured through western blotting. 3-BrPA inhibited cell proliferation, downregulated c-Myc and HK2 expression, and upregulated TXNIP expression in TNBC cells, but it doesn't have the same effect on non-TNBC cells. Furthermore, 3-BrPA induced the typical manifestations of mitochondrial-mediated apoptosis such as decreasing Bcl-2 expression and increasing Bax, Cyt-C and Caspase-3 expression. The present results suggested that 3-BrPA promoted TXNIP protein expression and reduced HK2 expression in TNBC cells by downregulating c-Myc expression, inhibiting glycolysis including suppressing lactate generation, intracellular ATP generation and HK activity, inducing mitochondrial-mediated apoptosis and eventually suppressing TNBC cell proliferation. These findings may reveal a novel therapeutic target for the clinical treatment of TNBC. |
| ISSN | 17920981 |
| Journal | Experimental and Therapeutic Medicine |
| Volume Number | 24 |
| PubMed Central reference number | PMC9257941 |
| Issue Number | 2 |
| PubMed reference number | 35837063 |
| e-ISSN | 17921015 |
| DOI | 10.3892/etm.2022.11447 |
| Language | English |
| Publisher | D.A. Spandidos |
| Publisher Date | 2022-06-16 |
| Access Restriction | Open |
| Rights License | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Li et al. |
| Subject Keyword | 3-bromopyruvic acid triple-negative breast cancer aerobic glycolysis c-Myc thioredoxin-interacting protein |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Microbiology Cancer Research |
