On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate
Many cancer cells display the Warburg effect, that is, enhanced glycolysis followed by fermentation (conversion of pyruvate to lactate). Recently, the molecular basis for these effects has started to be elucidated, and the upregulation of the lactate dehydrogenase A (LDH-A) isoform of lactate dehydr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-01-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558611801120 |
| _version_ | 1811247472414031872 |
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| author | Pankaj Seth Aaron Grant Jian Tang Elena Vinogradov Xioaen Wang Robert Lenkinski Vikas P. Sukhatme |
| author_facet | Pankaj Seth Aaron Grant Jian Tang Elena Vinogradov Xioaen Wang Robert Lenkinski Vikas P. Sukhatme |
| author_sort | Pankaj Seth |
| collection | DOAJ |
| description | Many cancer cells display the Warburg effect, that is, enhanced glycolysis followed by fermentation (conversion of pyruvate to lactate). Recently, the molecular basis for these effects has started to be elucidated, and the upregulation of the lactate dehydrogenase A (LDH-A) isoform of lactate dehydrogenase is felt to be a major molecular mediator of this phenomenon. Moreover, LDH-A expression in tumor tissue and LDH-A levels in blood portend a bad prognosis, and LDH-A blockade can lead to tumor growth inhibition in tumor transplant models. We have extended existing data (some of which were published during the time when we were carrying out our studies) in two important ways: 1) inhibition of LDH-A in a glycolytic lung cancer cell line results in reactive oxygen species– mediated apoptosis and increased sensitivity to the chemotherapeutic drug paclitaxel and 2) inhibition of fermentative glycolysis can also be accomplished by activation of the pyruvate dehydrogenase complex by the drug dichloroacetate, now undergoing clinical trials, and that this phenomenon can be monitored in vivo in a noninvasive real-time manner through magnetic resonance spectroscopy using hyperpolarized pyruvate. Collectively, these data suggest that in vivo effects of drugs that redirect the fate of pyruvate, and hence are aimed at reversing the Warburg effect, could be monitored through the use of hyperpolarized magnetic resonance spectroscopy, a method that is scalable to human use. |
| first_indexed | 2024-04-12T15:09:21Z |
| format | Article |
| id | doaj.art-fdcb5cfc0a074f4b8166eeb7a85552bd |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-04-12T15:09:21Z |
| publishDate | 2011-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-fdcb5cfc0a074f4b8166eeb7a85552bd2022-12-22T03:27:49ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-01-01131607110.1593/neo.101020On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized PyruvatePankaj SethAaron GrantJian TangElena VinogradovXioaen WangRobert LenkinskiVikas P. SukhatmeMany cancer cells display the Warburg effect, that is, enhanced glycolysis followed by fermentation (conversion of pyruvate to lactate). Recently, the molecular basis for these effects has started to be elucidated, and the upregulation of the lactate dehydrogenase A (LDH-A) isoform of lactate dehydrogenase is felt to be a major molecular mediator of this phenomenon. Moreover, LDH-A expression in tumor tissue and LDH-A levels in blood portend a bad prognosis, and LDH-A blockade can lead to tumor growth inhibition in tumor transplant models. We have extended existing data (some of which were published during the time when we were carrying out our studies) in two important ways: 1) inhibition of LDH-A in a glycolytic lung cancer cell line results in reactive oxygen species– mediated apoptosis and increased sensitivity to the chemotherapeutic drug paclitaxel and 2) inhibition of fermentative glycolysis can also be accomplished by activation of the pyruvate dehydrogenase complex by the drug dichloroacetate, now undergoing clinical trials, and that this phenomenon can be monitored in vivo in a noninvasive real-time manner through magnetic resonance spectroscopy using hyperpolarized pyruvate. Collectively, these data suggest that in vivo effects of drugs that redirect the fate of pyruvate, and hence are aimed at reversing the Warburg effect, could be monitored through the use of hyperpolarized magnetic resonance spectroscopy, a method that is scalable to human use.http://www.sciencedirect.com/science/article/pii/S1476558611801120 |
| spellingShingle | Pankaj Seth Aaron Grant Jian Tang Elena Vinogradov Xioaen Wang Robert Lenkinski Vikas P. Sukhatme On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate Neoplasia: An International Journal for Oncology Research |
| title | On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate |
| title_full | On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate |
| title_fullStr | On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate |
| title_full_unstemmed | On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate |
| title_short | On-target Inhibition of Tumor Fermentative Glycolysis as Visualized by Hyperpolarized Pyruvate |
| title_sort | on target inhibition of tumor fermentative glycolysis as visualized by hyperpolarized pyruvate |
| url | http://www.sciencedirect.com/science/article/pii/S1476558611801120 |
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