| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Seahorse Bioscience, Billerica, Michigan, United States
2 Seahorse Bioscience, Billerica, Massachusetts, United States
3 Seahorse Bioscience, Billerica, Michigan, United States; Billerica, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: mwu{at}seahorsebio.com.
Increased conversion of glucose to lactic acid associated with decreased mitochondrial respiration is a unique feature of tumors first described by Otto Warburg in the 1920s. Recent evidence suggests that the Warburg effect is caused by oncogenes and is an underlying mechanism of malignant transformation. Using a novel approach to measure cellular metabolic rates in vitro, the bioenergetic basis of this increased glycolysis and reduced mitochondrial respiration was investigated in two human cancer cell lines, H460 and A549. The bioenergetic phenotype was analyzed by measuring cellular respiration, glycolysis rate and ATP turnover of the cells in response to various pharmacological modulators. H460 and A549 cells displayed a dependency on glycolysis and an ability to significantly upregulate this pathway when their respiration was inhibited. The converse, however, was not true. The cell lines were attenuated in oxidative phosphorylation (OXPHOS) capacity and unable to sufficiently upregulate mitochondrial OXPHOS when glycolysis was disabled. This observed mitochondrial impairment was intimately linked to the increased dependency on glycolysis. Furthermore, it was demonstrated that H460 cells were more glycolytic, having a greater impairment of mitochondrial respiration, compared to A549 cells. Lastly, the upregulation of glycolysis in response to mitochondrial ATP synthesis inhibition was dependent on AMP-activated protein kinase activity. In summary, our results demonstrate a bioenergetic phenotype of these two cancer cell lines characterized by increased rate of glycolysis and a linked attenuation in their OXPHOS capacity. These metabolic alterations provide a mechanistic explanation for the growth advantage and apoptotic resistance of tumor cells.
This article has been cited by other articles:
|
|
 |
|
  N. Wu, L. Yin, E. A. Hanniman, S. Joshi, and M. A. Lazar Negative feedback maintenance of heme homeostasis by its receptor, Rev-erb{alpha} Genes & Dev., September 15, 2009; 23(18): 2201 - 2209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wu Real-Time Measurement of Mitochondrial Respiration and Glycolysis Rates of Cancer Cells in a Microplate Am. Assoc. Cancer Res. Educ. Book, April 18, 2009; 2009(1): 295 - 300. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pelicano, W. Lu, Y. Zhou, W. Zhang, Z. Chen, Y. Hu, and P. Huang Mitochondrial Dysfunction and Reactive Oxygen Species Imbalance Promote Breast Cancer Cell Motility through a CXCL14-Mediated Mechanism Cancer Res., March 15, 2009; 69(6): 2375 - 2383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xie, V. A. Valera, M. J. Merino, A. M. Amato, S. Signoretti, W. M. Linehan, V. P. Sukhatme, and P. Seth LDH-A inhibition, a therapeutic strategy for treatment of hereditary leiomyomatosis and renal cell cancer Mol. Cancer Ther., March 1, 2009; 8(3): 626 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Kiebish, X. Han, H. Cheng, J. H. Chuang, and T. N. Seyfried Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer J. Lipid Res., December 1, 2008; 49(12): 2545 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Gillies, I. Robey, and R. A. Gatenby Causes and Consequences of Increased Glucose Metabolism of Cancers J. Nucl. Med., June 1, 2008; 49(Suppl_2): 24S - 42S. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
