Clinical Study of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers

Linda L. Garland, José Guillen-Rodriguez, Chiu Hsieh Hsu, Lisa E. Davis, Eva Szabo, Christopher R. Husted, Hanqiao Liu, Ashley Leclerc, Yuriy O. Alekseyev, Gang Liu, Julie E. Bauman, Avrum E. Spira, Jennifer Beane, Malgorzata Wojtowicz, H. H.Sherry Chow

Research output: Contribution to journalArticlepeer-review

Abstract

The chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.

Original languageEnglish (US)
Article number2893
JournalCancers
Volume14
Issue number12
DOIs
StatePublished - Jun 1 2022
Externally publishedYes

Keywords

  • aspirin
  • cancer prevention
  • leukotriene
  • lung cancer
  • prostaglandin
  • zileuton

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Clinical Study of Aspirin and Zileuton on Biomarkers of Tobacco-Related Carcinogenesis in Current Smokers'. Together they form a unique fingerprint.

Cite this