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Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia

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Abstract

Breast cancer cells can survive and proliferate under harsh conditions of nutrient deprivation, including limited oxygen and glucose availability. We hypothesized that such environments trigger metabolic adaptations of mitochondria, which promote tumor progression. Here, we mimicked aglycemia and hypoxia in vitro and compared the mitochondrial and cellular bioenergetic adaptations of human breast cancer (HTB-126) and non-cancer (HTB-125) cells that originate from breast tissue. Using high-resolution respirometry and western blot analyses, we demonstrated that 4 days of glucose deprivation elevated oxidative phosphorylation five-fold, increased the spread of the mitochondrial network without changing its shape, and decreased the apparent affinity of oxygen in cancer cells (increase in C 50 ), whereas it remained unchanged in control cells. The substrate control ratios also remained constant following adaptation. We also observed the Crabtree effect, specifically in HTB-126 cells. Likewise, sustained hypoxia (1% oxygen during 6 days) improved cell respiration in non-cancer cells grown in glucose or glucose-deprived medium (+ 32% and +38%, respectively). Conversely, under these conditions of limited oxygen or a combination of oxygen and glucose deprivation for 6 days, routine respiration was strongly reduced in cancer cells (−36% in glucose medium, −24% in glucose-deprived medium). The data demonstrate that cancer cells behave differently than normal cells when adapting their bioenergetics to microenvironmental conditions. The differences in hypoxia and aglycemia tolerance between breast cancer cells and non-cancer cells may be important when optimizing strategies for the treatment of breast cancer.

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Authors and Affiliations

  1. INSERM U688, Bordeaux, France

    Katarína Smolková, Nadège Bellance & Rodrigue Rossignol

  2. Université Victor Segalen Bordeaux 2, Bordeaux, France

    Katarína Smolková, Nadège Bellance & Rodrigue Rossignol

  3. OROBOROS INSTRUMENTS, Innsbruck, Austria

    Francesca Scandurra

  4. INSERM U889, IECB, Pessac, France

    Elisabeth Génot

  5. Department of General and Transplant Surgery, D. Swarovski Research Laboratory, Medical University of Innsbruck, Innsbruck, Austria

    Erich Gnaiger

  6. Institute of Physiology, Dept. 75, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Katarína Smolková, Lydie Plecitá-Hlavatá & Petr Ježek

Authors
  1. Katarína Smolková
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  2. Nadège Bellance
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  3. Francesca Scandurra
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  4. Elisabeth Génot
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  5. Erich Gnaiger
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  6. Lydie Plecitá-Hlavatá
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  7. Petr Ježek
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  8. Rodrigue Rossignol
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Correspondence to Rodrigue Rossignol.

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Smolková, K., Bellance, N., Scandurra, F. et al. Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia. J Bioenerg Biomembr 42, 55–67 (2010). https://doi.org/10.1007/s10863-009-9267-x

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  • DOI: https://doi.org/10.1007/s10863-009-9267-x

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