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Warburg effect, anticancer drugs

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Life Science
LIFE 210
Paul Laybourn

12 October Overview Recap of the Warburg Effect First described by Otto Warburg and coworkers in 1927 Tumor and cancer cells Increased glucose uptake and lactate production relative to normal cells With normal O levels 2 Termed “aerobic glycolysis” In the brain, astrocytes and neuronal cells form a commensal metabolic relationship Astrocytes – “aerobic glycolysis” Neurons import lactate, use for oxidative phosphorylation Neurons also convert glutamine to glutamate, release as neurotransmitter Astrocytes convert glutamate to glutamine (toxic) In early embryogenesis First three cell divisions – “aerobic glycolysis” After that use both “aerobic glycolysis” and oxidative phosphorylation Embryonic cells also use glutamine to fill up the TCA cycle and produce amino acids, etc. Radiolabeled fluoro-2-deoxylgucose in positron emission tomography (PET) Shows high glucose uptake in cancer cells compared to normal cells Have found cancer cells also need a lot of glutamine Cancer cells have changes that short circuit the normal inhibition of glycolysis at normal O l2vels Tumor cells with poor blood supply and low O app2ar to have a commensal relationship with other (cancer or normal) cells with adequate O 2 Cancer cells with “aerobic glycolysis” also have high oxidative phosphorylation levels Cancer cells rely on glutamine for filling up the TCA cycle and producing amino acids, etc. More research is needed to better understand the other metabolic changes that occur in cancer cells. Targeting Cancer Cells Through the Warburg Effect Cancer cells (vs. normal cells) have unregulated growth and cell division Independent of actual nutrient supply “Addicted” to nutrients If nutrients inadequate Autophagy Cell death So, key metabolic enzyme inhibitors could be anticancer drugs When glucose first ente
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