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- Title
Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence
- Authors
Sukhatme, Vikas P.; Chan, Barden
- Abstract
Abstract: We show that knockdown of 6-phosphogluconate dehydrogenase (6PGD) of the pentose phosphate pathway (PPP) inhibits growth of lung cancer cells by senescence induction. This inhibition is not due to a defect in the oxidative PPP per se. NADPH and ribose phosphate production are normal in 6PGD knockdown cells and shutdown of PPP by knockdown of glucose-6-phosphate dehydrogenase (G6PD) has little effect on cell growth. Moreover, 6PGD knockdown cells can proliferate when the PPP is bypassed by using fructose instead of glucose in medium. Significantly, G6PD knockdown rescues proliferation of cells lacking 6PGD, suggesting an accumulation of growth inhibitory glucose metabolics in cells lacking 6PGD. Therefore, 6PGD inhibition may provide a novel strategy to treat glycolyic tumors such as lung cancer.
- Subjects
CANCER cells; PENTOSE phosphate pathway; LUNG cancer; GLUCOSE-6-phosphate dehydrogenase; CELL proliferation; OXIDATIVE stress
- Publication
FEBS Letters, 2012, Vol 586, Issue 16, p2389
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2012.05.052