Reduced Warburg Effect in Cancer Cells Undergoing Autophagy: Steady- State .sup.1H-MRS and Real-Time Hyperpolarized .sup.13C-MRS Studies

Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid depr...

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Bibliographic Details
Published in:PloS one 2014-03, Vol.9 (3), p.e92645
Main Authors: Lin, Gigin, Andrejeva, Gabriela, Wong Te Fong, Anne-Christine, Hill, Deborah K, Orton, Matthew R, Parkes, Harry G, Koh, Dow-Mu, Robinson, Simon P, Leach, Martin O, Eykyn, Thomas R, Chung, Yuen-Li
Format: Article
Language:English
Subjects:
Cancer
Cancer cells
Nuclear magnetic resonance spectroscopy
Physiological aspects
Proteins
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Summary:Autophagy is a highly regulated, energy dependent cellular process where proteins, organelles and cytoplasm are sequestered in autophagosomes and digested to sustain cellular homeostasis. We hypothesized that during autophagy induced in cancer cells by i) starvation through serum and amino acid deprivation or ii) treatment with PI-103, a class I PI3K/mTOR inhibitor, glycolytic metabolism would be affected, reducing flux to lactate, and that this effect may be reversible. We probed metabolism during autophagy in colorectal HT29 and HCT116 Bax knock-out cells using hyperpolarized .sup.13 C-magnetic resonance spectroscopy (MRS) and steady-state .sup.1 H-MRS. 24 hr PI103-treatment or starvation caused significant reduction in the apparent forward rate constant (k.sub.PL) for pyruvate to lactate exchange compared with controls in HT29 (100 [mu]M PI-103: 82%, p = 0.05) and HCT116 Bax-ko cells (10 [mu]M PI-103: 53%, p = 0.05; 20 [mu]M PI-103: 42%, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0092645