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3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

  • Authors:
    • Ting-An Wang
    • Xiao-Dong Zhang
    • Xing-Yu Guo
    • Shu-Lin Xian
    • Yun-Fei Lu
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1287-1296
    |
    Published online on: December 23, 2015
       https://doi.org/10.3892/or.2015.4511
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Abstract

Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.
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Copy and paste a formatted citation
Spandidos Publications style
Wang T, Zhang X, Guo X, Xian S and Lu Y: 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth. Oncol Rep 35: 1287-1296, 2016.
APA
Wang, T., Zhang, X., Guo, X., Xian, S., & Lu, Y. (2016). 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth. Oncology Reports, 35, 1287-1296. https://doi.org/10.3892/or.2015.4511
MLA
Wang, T., Zhang, X., Guo, X., Xian, S., Lu, Y."3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth". Oncology Reports 35.3 (2016): 1287-1296.
Chicago
Wang, T., Zhang, X., Guo, X., Xian, S., Lu, Y."3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth". Oncology Reports 35, no. 3 (2016): 1287-1296. https://doi.org/10.3892/or.2015.4511
Copy and paste a formatted citation
x
Spandidos Publications style
Wang T, Zhang X, Guo X, Xian S and Lu Y: 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth. Oncol Rep 35: 1287-1296, 2016.
APA
Wang, T., Zhang, X., Guo, X., Xian, S., & Lu, Y. (2016). 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth. Oncology Reports, 35, 1287-1296. https://doi.org/10.3892/or.2015.4511
MLA
Wang, T., Zhang, X., Guo, X., Xian, S., Lu, Y."3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth". Oncology Reports 35.3 (2016): 1287-1296.
Chicago
Wang, T., Zhang, X., Guo, X., Xian, S., Lu, Y."3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth". Oncology Reports 35, no. 3 (2016): 1287-1296. https://doi.org/10.3892/or.2015.4511
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