Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia |
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Authors: | Katarína Smolková Nadège Bellance Francesca Scandurra Elisabeth Génot Erich Gnaiger Lydie Plecitá-Hlavatá Petr Je?ek Rodrigue Rossignol |
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Institution: | (1) Institute of Analytical Chemistry, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, 81237 Bratislava, Slovakia;(2) Institute of Biochemistry, Nutrition and Health Protection, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, 81237 Bratislava, Slovakia;(3) Private Secondary Technical School ELBA, Smetanova 2, 08001 Prešov, Slovakia |
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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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