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Article

Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells

  • Authors:
    • Xue Zou
    • Mengxiao Zhang
    • Yiming Sun
    • Surong Zhao
    • Yingmei Wei
    • Xudong Zhang
    • Chenchen Jiang
    • Hao Liu
  • View Affiliations / Copyright

    Affiliations: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233004, P.R. China, Priority Research Center for Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia
  • Pages: 1895-1904
    |
    Published online on: July 23, 2015
       https://doi.org/10.3892/or.2015.4147
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Abstract

Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.
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Copy and paste a formatted citation
Spandidos Publications style
Zou X, Zhang M, Sun Y, Zhao S, Wei Y, Zhang X, Jiang C and Liu H: Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells. Oncol Rep 34: 1895-1904, 2015.
APA
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X. ... Liu, H. (2015). Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells. Oncology Reports, 34, 1895-1904. https://doi.org/10.3892/or.2015.4147
MLA
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X., Jiang, C., Liu, H."Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells". Oncology Reports 34.4 (2015): 1895-1904.
Chicago
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X., Jiang, C., Liu, H."Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells". Oncology Reports 34, no. 4 (2015): 1895-1904. https://doi.org/10.3892/or.2015.4147
Copy and paste a formatted citation
x
Spandidos Publications style
Zou X, Zhang M, Sun Y, Zhao S, Wei Y, Zhang X, Jiang C and Liu H: Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells. Oncol Rep 34: 1895-1904, 2015.
APA
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X. ... Liu, H. (2015). Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells. Oncology Reports, 34, 1895-1904. https://doi.org/10.3892/or.2015.4147
MLA
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X., Jiang, C., Liu, H."Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells". Oncology Reports 34.4 (2015): 1895-1904.
Chicago
Zou, X., Zhang, M., Sun, Y., Zhao, S., Wei, Y., Zhang, X., Jiang, C., Liu, H."Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells". Oncology Reports 34, no. 4 (2015): 1895-1904. https://doi.org/10.3892/or.2015.4147
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