Evidence for colorectal cancer cell specificity of aspirin effects on NFκB signalling and apoptosis

Epidemiological evidence indicates that non-steroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) to a greater degree than other non-gastrointestinal cancers, but the molecular basis for this difference is unknown. We previously reported that aspirin induces signal-specific IκBα degradation followed by NFκB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. Here, we explored the hypothesis that cell-type specific effects on NFκB signalling are responsible for the observed differences in protection by aspirin against CRC compared to breast and gynaecological cancers. We also assessed whether COX-2 expression, mutation status of adenomatous polyposis coli (APC), β-catenin, p53, or DNA mismatch repair (MMR) genes in CRC lines influenced aspirin-induced effects. We found that aspirin induced concentration-dependent IκBα degradation, NFκB nuclear translocation and apoptosis in all CRC lines studied. However, there was no such effect on the other cancer cell types, indicating a considerable degree of cell-type specificity. The lack of effect on NFκB signalling, paralleled by absence of an apoptotic response to aspirin in non-CRC lines, strongly suggests a molecular rationale for the particular protective effect of NSAIDs against CRC. Effects on NFκB and apoptosis were observed irrespective of COX-2 expression, or mutation status in APC, β-catenin, p53 and DNA MMR genes, underscoring the generality of the aspirin effect on NFκB in CRC cells. These findings raise the possibility of cell-type specific targets for the development of novel chemopreventative agents.

• Publication year

  2004

• Venue

  British Journal of Cancer

• Publication date

  2004-06-08

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/sj.bjc.6601913PMID 15188000PMCID 2409803
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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