Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells

Kah Tan Allen, Helen Chin-Sinex, Thomas DeLuca, Joseph R. Pomerening, Jeremy Sherer, John B. Watkins, John Foley, Jerry M. Jesseph, Marc Mendonca

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We investigated whether altering Warburg metabolism (aerobic glycolysis) by treatment with the metabolic agent dichloroacetate (DCA) could increase the X-ray-induced cell killing of the radiation-resistant human non-small-cell lung cancer (NSCLC) cell lines A549 and H1299. Treatment with 50 mM DCA decreased lactate production and glucose consumption in both A549 and H1299, clear indications of attenuated aerobic glycolysis. In addition, we found that DCA treatment also slowed cell growth, increased population-doubling time, and altered cell cycle distribution. Furthermore, we report that treatment with 50 mM DCA significantly increased single and fractionated X-ray-induced cell killing of A549 and H1299 cells. Assay of DNA double-strand break repair by neutral comet assays demonstrated that DCA inhibited both the fast and the slow kinetics of X-ray-induced DSB repair in both A549 and H1299 NSCL cancer cells. Taken together the data suggest a correlation between an attenuated aerobic glycolysis and enhanced cytotoxicity and radiation-induced cell killing in radiation-resistant NSCLC cells.

Original languageEnglish (US)
Article number12539
Pages (from-to)263-273
Number of pages11
JournalFree Radical Biology and Medicine
Volume89
DOIs
StatePublished - Dec 1 2015

Fingerprint

Cell growth
Metabolism
Lung Neoplasms
Cells
X-Rays
X rays
Glycolysis
Growth
Radiation
Non-Small Cell Lung Carcinoma
Assays
Repair
Comet Assay
Double-Stranded DNA Breaks
Population Growth
Cytotoxicity
Lactic Acid
Cell Cycle
Glucose
Kinetics

Keywords

  • Dichloroacetate (DCA)
  • Double-strand DNA break repair
  • Fractionated/split-dose
  • Non-small cell lung cancer (NSCLC)
  • Warburg effect

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells. / Tan Allen, Kah; Chin-Sinex, Helen; DeLuca, Thomas; Pomerening, Joseph R.; Sherer, Jeremy; Watkins, John B.; Foley, John; Jesseph, Jerry M.; Mendonca, Marc.

In: Free Radical Biology and Medicine, Vol. 89, 12539, 01.12.2015, p. 263-273.

Research output: Contribution to journalArticle

Tan Allen, Kah ; Chin-Sinex, Helen ; DeLuca, Thomas ; Pomerening, Joseph R. ; Sherer, Jeremy ; Watkins, John B. ; Foley, John ; Jesseph, Jerry M. ; Mendonca, Marc. / Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells. In: Free Radical Biology and Medicine. 2015 ; Vol. 89. pp. 263-273.
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