A unique glucose-dependent apoptotic pathway induced by c-Myc

Hyunsuk Shim, Yoon S. Chun, Brian C. Lewis, Chi V. Dang

Research output: Contribution to journalArticlepeer-review

Abstract

The lactate dehydrogenase A (LDH-A) gene, whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, has been identified as a c-Myc-responsive gene. It was of interest, therefore, to compare the effect of glucose deprivation in c-Myc-transformed and nontransformed cells. We observed that glucose deprivation or treatment with the glucose anti-metabolite 2-deoxyglucose caused nontransformed cells to arrest in the G0/G1 phase of the cell cycle. In contrast, c-Myc-transformed fibroblasts, lymphoblastoid, or lung carcinoma cells underwent extensive apoptosis. Ectopic expression of LDH-A alone in Rat1a fibroblasts was sufficient to induce apoptosis with glucose deprivation but not with serum withdrawal, suggesting that LDH-A mediates the unique apoptotic effect of c- Myc when glycolysis is blocked. The apoptosis caused by glucose deprivation was blocked by Bcl-2 expression but appeared to be independent of wild-type p53 activity. These studies provide insights on the coupling of glucose metabolism and the cell cycle in c-Myc-transformed cells and may in the future be exploited for cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)1511-1516
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998

Keywords

  • Apoptosis
  • Glucose deprivation
  • Lactate dehydrogenase

ASJC Scopus subject areas

  • Genetics
  • General

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