Tumor Biology

, Volume 37, Issue 5, pp 6661–6671 | Cite as

Nutrient deprivation-related OXPHOS/glycolysis interconversion via HIF-1α/C-MYC pathway in U251 cells

  • Zhongjian Liu
  • Yang Sun
  • Shirui Tan
  • Liang Liu
  • Suqiong Hu
  • Hongyu Huo
  • Meizhang Li
  • Qinghua Cui
  • Min YuEmail author
Original Article


Although the Warburg effect is a dominant metabolic phenotype observed in cancers, the metabolic changes and adaptation occurring in tumors have been demonstrated to extend beyond the Warburg effect and thus considered a secondary effect to the transformation process of carcinogenesis, including nutritional deficiencies. However, the role of nutritional deficiencies in this metabolic reprogramming (e. g., oxidative phosphorylation (OXPHOS)/glycolysis interconversion) is not completely known yet. Here, we showed that under regular culture condition, the proliferation of U251 cells, but not other tumor cell lines, preferentially performed the Warburg effect and was remarkably inhibited by oxamic acid which can inhibit the activity of lactate dehydrogenase (LDH); whereas under serum starvation, glycolysis was depressed, tricarboxylic acid cycle (TCA) was enhanced, and the activity of OXPHOS was reinforced to maintain cellular ATP content in a high level, but interestingly, we observed a decreased expression of reactive oxygen species (ROS). Moreover, the upregulated activity of mitochondrial complex I was confirmed by Western blots and showed that the mitochondrial-related protein, NDUFA9, NDUFB8, ND1, and VDAC1 were remarkably increased after serum starved. Mechanistically, nutritional deficiencies could reduce hypoxia-inducible factor α (HIF-1α) protein expression to increase C-MYC protein level, which in turn increased nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) transcription to enhance the activity of OXPHOS, suggesting that metabolic reprogramming by the changes of microenvironment during the carcinogenesis can provide some novel therapeutic clues to traditional cancer treatments.


Starvation OXPHOS Glycolysis HIF-1α C-MYC 



We would like to thank all the members of our laboratory for the encouragement and help in this study. This work was financially supported by the National Natural Science Foundation of China (no. 31260276, no. 31160237, and no. 81271330), the talent program of Yunnan Province (no. W8110305), and the Yunnan Province Science and Technology Innovation Team (no. 2011CI123)

Authors’ contributions

ZJL, YS, and MY designed the experiments with valuable help from QHC, MZL, HUH and ZJL performed and analyzed data with valuable help from ST and LL, and ZJL wrote the manuscript. ZJL and MY oversaw the overall project.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhongjian Liu
    • 1
    • 2
    • 3
  • Yang Sun
    • 1
    • 2
  • Shirui Tan
    • 1
    • 2
  • Liang Liu
    • 1
    • 2
  • Suqiong Hu
    • 1
    • 2
  • Hongyu Huo
    • 1
    • 2
  • Meizhang Li
    • 1
    • 2
  • Qinghua Cui
    • 1
    • 2
  • Min Yu
    • 1
    • 2
    Email author
  1. 1.Laboratory of Biochemistry and Molecular Biology, School of Life SciencesYunnan UniversityKunmingChina
  2. 2.Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life SciencesYunnan UniversityKunmingChina
  3. 3.Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic MedicineSichuan UniversityChengduChina

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