Tumor Biology

, Volume 37, Issue 2, pp 1727–1738 | Cite as

Aspirin and salicylic acid decrease c-Myc expression in cancer cells: a potential role in chemoprevention

  • Guoqiang Ai
  • Rakesh Dachineni
  • Pratik Muley
  • Hemachand Tummala
  • G. Jayarama Bhat
Original Article

Abstract

Epidemiological studies have demonstrated a significant correlation between regular aspirin use and reduced colon cancer incidence and mortality; however, the pathways by which it exerts its anti-cancer effects are still not fully explored. We hypothesized that aspirin’s anti-cancer effect may occur through downregulation of c-Myc gene expression. Here, we demonstrate that aspirin and its primary metabolite, salicylic acid, decrease the c-Myc protein levels in human HCT-116 colon and in few other cancer cell lines. In total cell lysates, both drugs decreased the levels of c-Myc in a concentration-dependent fashion. Greater inhibition was observed in the nucleus than the cytoplasm, and immunofluorescence studies confirmed these observations. Pretreatment of cells with lactacystin, a proteasome inhibitor, partially prevented the downregulatory effect of both aspirin and salicylic acid, suggesting that 26S proteasomal pathway is involved. Both drugs failed to decrease exogenously expressed DDK-tagged c-Myc protein levels; however, under the same conditions, the endogenous c-Myc protein levels were downregulated. Northern blot analysis showed that both drugs caused a decrease in c-Myc mRNA levels in a concentration-dependent fashion. High-performance liquid chromatography (HPLC) analysis showed that aspirin taken up by cells was rapidly metabolized to salicylic acid, suggesting that aspirin’s inhibitory effect on c-Myc may occur through formation of salicylic acid. Our result suggests that salicylic acid regulates c-Myc level at both transcriptional and post-transcription levels. Inhibition of c-Myc may represent an important pathway by which aspirin exerts its anti-cancer effect and decrease the occurrence of cancer in epithelial tissues.

Keywords

Aspirin Salicylic acid c-Myc Proteasome Colon cancer 

Notes

Acknowledgments

Support from the Translational Cancer Research Seed Grant, funded as 2010 Research Initiative Center by the State of South Dakota, Faculty Excellence Fund from South Dakota State University and from NIH (5RO3CA133061-02) to GJB is gratefully acknowledged. We also thank Dr. LLoyd Alfonso, D’Youville College (School of Pharmacy), Buffalo, NY and Ms. Yang Yang, South Dakota State University, for helpful discussions.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Guoqiang Ai
    • 1
  • Rakesh Dachineni
    • 1
  • Pratik Muley
    • 1
  • Hemachand Tummala
    • 1
  • G. Jayarama Bhat
    • 1
  1. 1.Department of Pharmaceutical SciencesSouth Dakota State University College of PharmacyBrookingsUSA

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