The Pro‐Apoptotic Effect of Glucose Restriction in NSCLC via AMPK‐Regulated Circadian Clock Gene Bmal1

May 20, 2025Cancer science

Glucose Restriction May Trigger Cell Death in Lung Cancer by Activating Energy Sensor and Body Clock Gene Bmal1

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Abstract

Glucose restriction significantly delayed tumor growth in a model of non-small cell lung cancer (NSCLC).

  • Circadian clock genes, such as Bmal1, play a key role in regulating in NSCLC cells.
  • Bmal1 is highly expressed in normal tissues and is associated with better prognosis in lung adenocarcinoma patients.
  • In NSCLC cells, higher Bmal1 expression correlates with increased activity of proapoptotic genes.
  • A glucose-restricted diet increased Bmal1 and proapoptotic gene expression in tumor xenograft models.
  • Findings suggest that glucose restriction may promote apoptosis in NSCLC through a mechanism involving Bmal1.

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Key numbers

11 mM
Increase in Pro-Apoptotic Gene Expression
Concentration of glucose in cell culture medium causing in NSCLC cells.
90% fat, 1.6% carbohydrate, 8.4% protein
Ketogenic Diet Impact on Tumor Growth
Macronutrient composition of the ketogenic diet used in mouse xenograft studies.
higher in normal tissue
Bmal1 Expression Correlation with Prognosis
Bmal1 expression levels in lung adenocarcinoma vs. normal lung tissue.

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