Open Access

3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells

  • Authors:
    • Jiachen Li
    • Jianmin Pan
    • Yang Liu
    • Xiaohui Luo
    • Cheng Yang
    • Wangfa Xiao
    • Qishang Li
    • Lihui Yang
    • Xiaodong Zhang
  • View Affiliations

  • Published online on: June 16, 2022     https://doi.org/10.3892/etm.2022.11447
  • Article Number: 520
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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August-2022
Volume 24 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Li J, Pan J, Liu Y, Luo X, Yang C, Xiao W, Li Q, Yang L and Zhang X: 3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells. Exp Ther Med 24: 520, 2022
APA
Li, J., Pan, J., Liu, Y., Luo, X., Yang, C., Xiao, W. ... Zhang, X. (2022). 3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells. Experimental and Therapeutic Medicine, 24, 520. https://doi.org/10.3892/etm.2022.11447
MLA
Li, J., Pan, J., Liu, Y., Luo, X., Yang, C., Xiao, W., Li, Q., Yang, L., Zhang, X."3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells". Experimental and Therapeutic Medicine 24.2 (2022): 520.
Chicago
Li, J., Pan, J., Liu, Y., Luo, X., Yang, C., Xiao, W., Li, Q., Yang, L., Zhang, X."3‑Bromopyruvic acid regulates glucose metabolism by targeting the c‑Myc/TXNIP axis and induces mitochondria‑mediated apoptosis in TNBC cells". Experimental and Therapeutic Medicine 24, no. 2 (2022): 520. https://doi.org/10.3892/etm.2022.11447