TY - JOUR
T1 - The cancer cell's "power plants" as promising therapeutic targets
T2 - An overview
AU - Pedersen, Peter L.
N1 - Funding Information:
Acknowledgements The author is most grateful for support from the NIH via research grants CA 80018 and CA 10951. He wishes to thank also Dr. Young H. Ko for many helpful discussions about cancer and the chemistry and mechanism of action of anticancer agents, and Dr. George H. Sack Jr. for critically reading the manuscript. David Blum, a predoctoral student in the Department of Biological Chemistry, Johns Hopkins University School of Medicine and a medical illustrator, is acknowledged for his help in preparing Figure A and B, and Dr. David Rini, an Associate Professor of Art as Applied to Medicine, Johns Hopkins University School of Medicine, is acknowledged for the art work in Fig. 2B (Left Panel). The author is also grateful to Elsevier for granting permission to reproduce Fig. 1B in slightly modified form from Ko et al. (2004) Biochem Biophys Res Commun 324:269-275, Copyright 2004.
PY - 2007/2
Y1 - 2007/2
N2 - This introductory article to the review series entitled "The Cancer Cell's Power Plants as Promising Therapeutic Targets" is written while more than 20 million people suffer from cancer. It summarizes strategies to destroy or prevent cancers by targeting their energy production factories, i.e., "power plants." All nucleated animal/human cells have two types of power plants, i.e., systems that make the "high energy" compound ATP from ADP and P i . One type is "glycolysis," the other the "mitochondria." In contrast to most normal cells where the mitochondria are the major ATP producers (>90%) in fueling growth, human cancers detected via Positron Emission Tomography (PET) rely on both types of power plants. In such cancers, glycolysis may contribute nearly half the ATP even in the presence of oxygen ("Warburg effect"). Based solely on cell energetics, this presents a challenge to identify curative agents that destroy only cancer cells as they must destroy both of their power plants causing "necrotic cell death" and leave normal cells alone. One such agent, 3-bromopyruvate (3-BrPA), a lactic acid analog, has been shown to inhibit both glycolytic and mitochondrial ATP production in rapidly growing cancers (Ko et al., Cancer Letts., 173, 83-91, 2001), leave normal cells alone, and eradicate advanced cancers (19 of 19) in a rodent model (Ko et al., Biochem. Biophys. Res. Commun., 324, 269-275, 2004). A second approach is to induce only cancer cells to undergo "apoptotic cell death." Here, mitochondria release cell death inducing factors (e.g., cytochrome c). In a third approach, cancer cells are induced to die by both apoptotic and necrotic events. In summary, much effort is being focused on identifying agents that induce "necrotic," "apoptotic" or apoptotic plus necrotic cell death only in cancer cells. Regardless how death is inflicted, every cancer cell must die, be it fast or slow.
AB - This introductory article to the review series entitled "The Cancer Cell's Power Plants as Promising Therapeutic Targets" is written while more than 20 million people suffer from cancer. It summarizes strategies to destroy or prevent cancers by targeting their energy production factories, i.e., "power plants." All nucleated animal/human cells have two types of power plants, i.e., systems that make the "high energy" compound ATP from ADP and P i . One type is "glycolysis," the other the "mitochondria." In contrast to most normal cells where the mitochondria are the major ATP producers (>90%) in fueling growth, human cancers detected via Positron Emission Tomography (PET) rely on both types of power plants. In such cancers, glycolysis may contribute nearly half the ATP even in the presence of oxygen ("Warburg effect"). Based solely on cell energetics, this presents a challenge to identify curative agents that destroy only cancer cells as they must destroy both of their power plants causing "necrotic cell death" and leave normal cells alone. One such agent, 3-bromopyruvate (3-BrPA), a lactic acid analog, has been shown to inhibit both glycolytic and mitochondrial ATP production in rapidly growing cancers (Ko et al., Cancer Letts., 173, 83-91, 2001), leave normal cells alone, and eradicate advanced cancers (19 of 19) in a rodent model (Ko et al., Biochem. Biophys. Res. Commun., 324, 269-275, 2004). A second approach is to induce only cancer cells to undergo "apoptotic cell death." Here, mitochondria release cell death inducing factors (e.g., cytochrome c). In a third approach, cancer cells are induced to die by both apoptotic and necrotic events. In summary, much effort is being focused on identifying agents that induce "necrotic," "apoptotic" or apoptotic plus necrotic cell death only in cancer cells. Regardless how death is inflicted, every cancer cell must die, be it fast or slow.
KW - 3-BrPA
KW - 3-bromopyruvate
KW - Anti-cancer agents
KW - Apoptosis
KW - Bioenergetics
KW - Cancer
KW - Cancer therapy
KW - Cell death
KW - Cytochrome c
KW - Energy metabolism
KW - Glycolysis
KW - Mitochondria
KW - Necrosis
KW - Power plants
KW - Warburg
KW - Warburg effect
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U2 - 10.1007/s10863-007-9070-5
DO - 10.1007/s10863-007-9070-5
M3 - Review article
C2 - 17404823
AN - SCOPUS:34249945104
SN - 0145-479X
VL - 39
SP - 1
EP - 12
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
IS - 1
ER -