Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells

Mariia Yuneva1, Nicola Zamboni, Peter Oefner

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Insights

Glucose deprivation kills normal human cells differently than cancer cells. Glutamine deprivation induces MYC-dependent apoptosis in cancer cells, suggesting glutamine metabolism is a potential therapeutic target.

Area of Science:

  • Cellular metabolism
  • Cancer biology
  • Apoptosis

Background:

  • Targeting cancer cell metabolism is a promising therapeutic strategy.
  • The proto-oncogene MYC influences cellular responses to nutrient deprivation.
  • Glucose and glutamine are key nutrients for cancer cell growth.

Purpose of the Study:

  • To investigate the differential effects of glucose and glutamine deprivation on normal human cells and MYC-expressing cancer cells.
  • To elucidate the mechanisms underlying nutrient-induced cell death.
  • To evaluate the potential of nutrient deprivation as a cancer therapy.

Main Methods:

  • Comparative analysis of normal human cells and MYC-transduced cells under glucose and glutamine deprivation.
  • Assessment of apoptosis induction and cell viability.
  • Measurement of Krebs cycle intermediates and ATP levels.

Main Results:

  • Glucose deprivation induced non-apoptotic cell death in normal human cells, independent of MYC.
  • Glutamine deprivation triggered MYC-dependent apoptosis in cancer cells.
  • This glutamine-induced apoptosis was linked to Krebs cycle disruption but not ATP depletion.

Conclusions:

  • Normal human cell responses to nutrient deprivation must be considered in cancer therapy development.
  • Glutamine metabolism's link to MYC-dependent apoptosis offers potential new therapeutic avenues for cancer treatment.

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