Radioprotection or radiosensitization? Unraveling caffeine's bifurcated effects on radiation-induced damage

Area of Science:

• Radiation biology
• Pharmacology
• Molecular oncology

Background:

• Caffeine is a widely consumed phytochemical with complex effects on cellular radiation responses.
• Its dual role as a radioprotector and radiosensitizer necessitates a deeper understanding of its mechanisms.

Purpose of the Study:

• To comprehensively review caffeine's interactions with ionizing and non-ionizing radiation.
• To elucidate the mechanisms underlying caffeine's context-dependent effects on normal and cancer cells.
• To evaluate caffeine's potential as an adjuvant in radiotherapy.

Main Methods:

• Synthesis of evidence from in vitro, in vivo, and clinical studies.
• Analysis of caffeine's influence on DNA repair, cell cycle arrest, and apoptosis.
• Review of preclinical data on tissue protection and clinical observations on radiotherapy toxicity.

Main Results:

• Caffeine inhibits DNA repair (ATM/ATR), overrides cell cycle arrest, and modulates apoptosis.
• It protects normal tissues by mitigating oxidative stress and reducing chromosomal aberrations.
• Caffeine sensitizes cancer cells by disrupting DNA repair and promoting mitotic catastrophe.

Conclusions:

• Caffeine's effects are highly context-dependent, varying with radiation type, dose, cell lineage, and timing.
• Preclinical studies show potential for attenuating radiation toxicity, but risks like chromosomal instability exist.
• Clinical evidence is sparse, suggesting caffeine's potential as a radiotherapy adjuvant requires careful, precise application and further research.