Synthesis and characterization of an aspirin-fumarate prodrug that inhibits NFκB activity and breast cancer stem cells

Irida Kastrati, Loruhama Delgado-Rivera, Gergana Georgieva, Gregory R.J. Thatcher, Jonna Frasor

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Inflammation is a cancer hallmark that underlies cancer incidence and promotion, and eventually progression to metastasis. Therefore, adding an anti-inflammatory drug to standard cancer regiments may improve patient outcome. One such drug, aspirin (acetylsalicylic acid, ASA), has been explored for cancer chemoprevention and anti-tumor activity. Besides inhibiting the cyclooxygenase 2-prostaglandin axis, ASA's anti-cancer activities have also been attributed to nuclear factor ĸB (NFĸB) inhibition. Because prolonged ASA use may cause gastrointestinal toxicity, a prodrug strategy has been implemented successfully. In this prodrug design the carboxylic acid of ASA is masked and additional pharmacophores are incorporated. This protocol describes how we synthesized an aspirin-fumarate prodrug, GTCpFE, and characterized its inhibition of the NFĸB pathway in breast cancer cells and attenuation of the cancer stem-like properties, an important NFĸB-dependent phenotype. GTCpFE effectively inhibits the NFĸB pathway in breast cancer cell lines whereas ASA lacks any inhibitory activity, indicating that adding fumarate to ASA structure significantly contributes to its activity. In addition, GTCpFE shows significant anti-cancer stem cell activity by blocking mammosphere formation and attenuating the cancer stem cell associated CD44+CD24- immunophenotype. These results establish a viable strategy to develop improved anti-inflammatory drugs for chemoprevention and cancer therapy.

Original languageEnglish (US)
Article numbere54798
JournalJournal of Visualized Experiments
Issue number119
StatePublished - Jan 18 2017
Externally publishedYes


  • Aspirin
  • Breast cancer
  • Cancer research
  • Cancer stem cells
  • Fumarate
  • Inflammation
  • Issue 119
  • Nuclear factor ĸB
  • Prodrug

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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