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Pharmaceutical Research

, 28:2731 | Cite as

Mitochondrial Metabolism Inhibitors for Cancer Therapy

  • Emma E. Ramsay
  • Philip J. Hogg
  • Pierre J. Dilda
Expert Review

ABSTRACT

Cancer cells catabolise nutrients in a different way than healthy cells. Healthy cells mainly rely on oxidative phosphorylation, while cancer cells employ aerobic glycolysis. Glucose is the main nutrient catabolised by healthy cells, while cancer cells often depend on catabolism of both glucose and glutamine. A key organelle involved in this altered metabolism is mitochondria. Mitochondria coordinate the catabolism of glucose and glutamine across the cancer cell. Targeting mitochondrial metabolism in cancer cells has potential for the treatment of this disease. Perhaps the most promising target is the hexokinase-voltage dependent anion channel-adenine nucleotide translocase complex that spans the outer- and inner-mitochondrial membranes. This complex links glycolysis, oxidative phosphorylation and mitochondrial-mediated apoptosis in cancer cells. This review discusses cancer cell mitochondrial metabolism and the small molecule inhibitors of this metabolism that are in pre-clinical or clinical development.

KEY WORDS

adenine nucleotide translocase cancer hexokinase metabolism mitochondria 

ABBREVIATIONS

alpha-TOS

alpha-tocopheryl succinate

ANT

adenine nucleotide translocase

ATP

adenosine triphosphate

CAO

4-(N-(S-cysteinylacetyl)amino) phenylarsonous acid

FADH2

flavin adenine dinucleotide

FH

fumarate hydratase

GCAO

4-(N-(S-cysteinylglycylacetyl)amino) phenylarsonous acid

G6P

glucose-6-phosphate

GLUT

glucose transporter

GPT

glutamate pyruvate transaminase

GSAO

4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid

HIF1

hypoxia inducible factor 1

IDH

isocitrate dehydrogenase

NADH

nicotinamide adenine dinucleotide (reduced)

NADPH

nicotinamide adenine dinucleotide phosphate (reduced)

NSCLC

non-small-cell lung carcinoma

PENAO

4-(N-(S-penicillaminylacetyl)amino)phenylarsonous acid

PDH

pyruvate dehydrogenase

PDHK

pyruvate dehydrogenase kinase

SDH

succinate dehydrogenase

TCA

tricarboxylic acid cycle

VDAC

voltage dependent anion channel

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Emma E. Ramsay
    • 1
  • Philip J. Hogg
    • 1
  • Pierre J. Dilda
    • 1
  1. 1.Prince of Wales Clinical School, Lowy Cancer Research CentreUniversity of New South WalesSydneyAustralia

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