Pleiotropic Effects of Caffeine Leading to Chromosome Instability and Cytotoxicity in Eukaryotic Microorganisms

J Microbiol Biotechnol. 2021 Feb 28;31(2):171-180. doi: 10.4014/jmb.2011.11042.


Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

Keywords: Caffeine; DNA damage checkpoint; growth inhibition; radiosensitization; unicellular eukaryotes.

Publication types

  • Review

MeSH terms

  • Caffeine / pharmacology*
  • Chromosomal Instability / drug effects
  • DNA Damage / drug effects
  • Eukaryota / drug effects*
  • Eukaryota / genetics*
  • Eukaryota / metabolism
  • Signal Transduction / drug effects


  • Caffeine