Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression

By A. Le, Charles R Cooper, A. Gouw, Ramani Dinavahi, A. Maitra, L. Deck, R. Royer, D. V. Vander Jagt, G. Semenza, C. V. Dang. Proceedings of the National Academy of Sciences of the United States of America, 2010

1,477 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a86ee4b76f43c4e96e9366bbbc4161b7a09d2cba

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. C. V. Dang
2. Navdeep S. Chandel
3. Ralph J. Deberardinis
4. M. V. Vander Heiden
5. Huafeng Zhang
6. Sophia Y. Lunt
7. Ming Tan
8. Ping Gao

In Molecular Biology

1. Navdeep S. Chandel
2. C. V. Dang
3. Ralph J. Deberardinis
4. M. V. Vander Heiden
5. Huafeng Zhang
6. Ming Tan
7. Ping Gao
8. Sophia Y. Lunt

Citations in the corpus

• The Warburg effect in tumor progression: Mitochondrial oxidative metabolism as an anti-metastasis mechanism (2014, background): “Inhibition of LDH re-directs pyruvate into mitochondrial oxidation [95].”
• Targeting lactate metabolism for cancer therapeutics. (2013, background): “In addition, FX-11, a gossypol derivative that shows selectivity for LDHA over LDHB ( K i of 0.05 vs. 20 μ M, respectively) (55), has antitumor activity in xenograft models and has the potential to be developed into a cancer therapeutic (37, 56).”
• Targeting mitochondrial glutaminase activity inhibits oncogenic transformation (2010, positive): “vidual days of treatment as described by Le et al. (2010).”
• Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression (2015, background): “Dang’s group has documented that inhibition of LDHA by a small-molecule inhibitor (FX11) restrains glycolysis and shunts pyruvate into the mitochondrion [52].”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “MYC regulates the expression of LDH-A (Shim et al 1997), and MYC-dependent tumors cannot proliferate when LDH-A expression is knocked down (Le et al 2010).”
• Drug resistance and combating drug resistance in cancer (2019, background): “For all the reasons mentioned above, inhibitors targeting glycolysis related proteins (GAPDH and LDH) like 3-bromopyruvate, oxamate and FX11 that significantly deplete intracellular ATP levels might sensitize cancer cells to anticancer drugs([170-174]).”
• c-Myc and Cancer Metabolism (2012, positive): “Inhibition of LDH-A has been shown to inhibit tumor progression (83).”
• Understanding the intersections between metabolism and cancer biology (2017, positive): “Dependence on the enzyme lactate dehydrogenase (LDH) was demonstrated both genetically and pharmacologically (Fantin et al., 2006; Le et al., 2010; Shim et al., 1997), leading to development of LDHA inhibitors (Boudreau et al., 2016), but none progressed to clinical trials, suggesting either…”
• Targeting cellular metabolism to improve cancer therapeutics (2013, methodology): “reduces ATP levels and induces significant oxidative stress resulting in cell death.(66) Importantly, combining FX11 with FK866, an NADþ synthesis inhibitor, induces lymphoma regression in a xenograft model (Table 1).”
• The Warburg Effect Dictates the Mechanism of Butyrate Mediated Histone Acetylation and Cell Proliferation (2012, background): “This knockdown is also known to increase oxygen consumption (Le et al., 2010).”
• Tumor glycolysis as a target for cancer therapy: progress and prospects (2013, background): “FX11, an inhibitor of LDH depletes intracellular ATP levels, which in turn significantly increase oxidative stress resulting in tumor cell death [110].”
• ROS homeostasis and metabolism: a dangerous liason in cancer cells (2016, background): “Also, inhibition of lactate dehydrogenase-A through the small-molecule FX11 impaired the malignant progression of lymphoma and pancreatic cancer xenografts by decreasing the intracellular ATP levels and inducing oxidative stress.(82) Late, the inhibition of glycolysis and the PPP combined with the d”
• MYC, metabolism, cell growth, and tumorigenesis. (2013, background): “This NADþ could be reused by glyceraldehyde 3phosphate dehydrogenase (GADPH), one of the intermediate steps of the glycolytic pathway, to maintain glycolytic flux (Le et al. 2010).”
• Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B-cells (2012, neutral): “into male SCID mice (National Cancer Institute) as previously described (Le et al., 2010).”