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The rate of aerobic glycolysis is a pivotal regulator of tumor progression

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Abstract

Purpose

Cancer cells depend on glucose metabolism via exclusive glycolysis pathway is named Aerobic glycolysis or Warburg effect. The aim of this study was investigation of different glucose accessibility conditions on the rate of Warburg effect and its impact on Hypoxia inducible factors-1 α (HIF-1 α)/vascular endothelium growth factor (VEGF) pathway in breast cancer cells lines.

Methods

MDA-MB-231 (Warburg phenomenon) and MCF-7 (oxidative) cell lines were cultured in DMEM and exposed to three different glucose accessibility medium for 48 h (5.5 mM as normal glucose (NG), 25 mM as high glucose (HG) and 2-Deoxyglucose (2-DG) as restricted glucose accessibility). Glucose uptake, intra/extracellular lactate and pyruvate, HIF-1α accumulation and vascular endothelium growth factor (VEGF) expression were evaluated by standard methods.

Results

Our results showed in NG condition both of cell lines produce lactate, but it was higher in MDA-MB-231. HG condition increased extracellular lactate in both cell lines especially in MCF-7 cells whereas intracellular lactate and pyruvate raised only in MCF-7. 2-DG decreased extracellular and intracellular lactate and pyruvate in both cell lines especially in MDA-MB-231. HIF-1α accumulation was detectable in NG condition in both cell lines. HG condition increased HIF-1α accumulation in MCF-7 cells but not in MDA-MB-231 and 2-DG decreased it in both call lines, especially in MDA-MB-231. Expression of VEGF had similar pattern with HIF-1α in different conditions.

Conclusions

Our findings revealed the rate of Warburg effect is an important indicator for tumor promotion and invasion due to its impacts on important transcription factors like HIF-1α.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

This work was performed in partial fulfillment of the requirements for Master of Clinical biochemistry of Mohammad Erfan Zare, under consultation of Prof. Asad Vaisi-Raygani in Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran (grant number: 91190).

Code availability

Not Applicable.

Funding

This work was supported by Kermanshah University of Medical Sciences on the Grant Number 91190. This funding’s devoted just to purchasing materials used in our study.

Author information

Authors and Affiliations

  1. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Erfan Zare, Atefeh Nasir Kansestani, Shahrooz Hemmati & Kamran Mansouri

  2. Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Erfan Zare

  3. Fertility and Infertility Research Center, Kermanshah University of Medical Sciences, Daneshgah Avenue, Kermanshah, 67148-69914, Iran

    Asad Vaisi-Raygani

Authors
  1. Mohammad Erfan Zare
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  2. Atefeh Nasir Kansestani
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  3. Shahrooz Hemmati
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  4. Kamran Mansouri
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  5. Asad Vaisi-Raygani
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Contributions

MEZ designed the study and performed all tests. ANK, SH and KM play role in project administration. AVR supervised all of the stages of designing the study, conducting the research, and writing the manuscript.

Corresponding author

Correspondence to Asad Vaisi-Raygani.

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All authors declare that they have no conflict of interest.

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Zare, M.E., Kansestani, A.N., Hemmati, S. et al. The rate of aerobic glycolysis is a pivotal regulator of tumor progression. J Diabetes Metab Disord 20, 523–531 (2021). https://doi.org/10.1007/s40200-021-00774-7

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  • DOI: https://doi.org/10.1007/s40200-021-00774-7

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