Antiproliferative Effect of Nonsteroidal Antiinflammatory Drugs Against Human Colon Cancer Cells

Lee J. Hixson, David S. Alberts, Mary Krutzsch, Janine Einsphar, Klaus Brendel, Paul H. Gross, Nancy Shipp Paranka, Monika Baier, Scott Emerson, Rifat Pamukcu, Randall W. Burt

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs, including two sulindac derivatives, against human colon cancer cells in vitro. Ht-29, SW480, and DLD-1 cells were continuously incubated with serial drug dilutions for 6 days prior to fixation. Cell number was determined using the sulforhodamine B assay, and drug concentrations which inhibited cell growth by 50% were estimated for each agent by interpolation. All drugs exhibited antiproliferative activity against Ht-29 and DLD-1 cells, and most inhibited SW480 cells. For Ht-29 cells, the 50% inhibitory concentration varied from 55 pM for diclofenac to 2100 pM for 5-aminosalicylic acid, with three drug groups of high, intermediate, and low potency evident. Inhibition of cell growth by sulindac sulfide was reversible following drug removal. Nonsteroidal antiinflammatory drugs exert an antiproliferative effect against human colon cancer cells with a wide range of potencies. A cytostatic response was demonstrated with sulindac sulfide. These data further support the potential role of these agents for chemoprevention of colorectal neoplasia.

Original languageEnglish (US)
Pages (from-to)433-438
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume3
Issue number5
StatePublished - Jul 1 1994

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Hixson, L. J., Alberts, D. S., Krutzsch, M., Einsphar, J., Brendel, K., Gross, P. H., Paranka, N. S., Baier, M., Emerson, S., Pamukcu, R., & Burt, R. W. (1994). Antiproliferative Effect of Nonsteroidal Antiinflammatory Drugs Against Human Colon Cancer Cells. Cancer Epidemiology Biomarkers and Prevention, 3(5), 433-438.