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Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
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Citrate oscillations during cell cycle are a targetable vulnerability in cancer cells
Philippe Icard1, Marco Alifano2, Luca Simula3
1Université de Normandie, UNICAEN, Inserm U1086 Interdisciplinary Research Unit for Cancer Prevention and Treatment, Caen, France; Thoracic Surgery Department, Cochin Hospital, APHP-Centre, Université Paris-Descartes, Paris, France.
Biochimica Et Biophysica Acta. Reviews on Cancer
|April 11, 2025
Summary
Cellular metabolism and the cell cycle are linked. Citrate levels oscillate during cell division, and dysregulation in cancer cells fuels tumor growth. Sodium citrate administration shows promise in cancer treatment.
Area of Science:
- Cell Biology
- Metabolic Regulation
- Cancer Research
Background:
- Cell cycle progression is tightly regulated by metabolic oscillations.
- Cytosolic citrate levels dynamically change throughout the cell cycle phases.
- Aberrant citrate metabolism is implicated in cancer progression.
Purpose of the Study:
- To elucidate the role of metabolic oscillations in cell cycle progression.
- To detail the dynamic regulation of cytosolic citrate during cell division.
- To explore the therapeutic potential of sodium citrate in cancer treatment.
Main Methods:
- Review of existing literature on cell cycle metabolism.
- Analysis of citrate dynamics across cell cycle phases.
- Examination of in vivo studies on sodium citrate administration in cancer models.
Main Results:
- Metabolic oscillations meet the bioenergetic demands of each cell cycle phase.
- Cytosolic citrate is low in G1, increases in S, peaks in G2/M, and decreases in mitosis.
- In cancer, dysregulated citrate supports the Warburg effect, PI3K/AKT signaling, and alternative acetyl-CoA production.
Conclusions:
- Sodium citrate administration arrests the cell cycle, inhibits glycolysis and PI3K/AKT, induces apoptosis, and reduces tumor growth.
- Citrate dysregulation in cancer promotes uncontrolled proliferation and oncogenic signaling.
- Citrate administration may enhance the efficacy of cell cycle inhibitors for improved cancer therapy.
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