The cancer cell's "power plants" as promising therapeutic targets: An overview

Peter L Pedersen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalJournal of Bioenergetics and Biomembranes
Volume39
Issue number1
DOIs
StatePublished - Feb 2007

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Power Plants
Neoplasms
Therapeutics
Cell Death
Mitochondria
Adenosine Triphosphate
Glycolysis
Cytochromes c
Positron-Emission Tomography
Adenosine Diphosphate

Keywords

  • 3-bromopyruvate
  • 3-BrPA
  • Anti-cancer agents
  • Apoptosis
  • Bioenergetics
  • Cancer
  • Cancer therapy
  • Cell death
  • Cytochrome c
  • Energy metabolism
  • Glycolysis
  • Mitochondria
  • Necrosis
  • Power plants
  • Warburg
  • Warburg effect

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

The cancer cell's "power plants" as promising therapeutic targets : An overview. / Pedersen, Peter L.

In: Journal of Bioenergetics and Biomembranes, Vol. 39, No. 1, 02.2007, p. 1-12.

Research output: Contribution to journalArticle

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