Skip to main content

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Cyclooxygenases, and the Cell Cycle

Their Interactions in Colon Cancer

  • Chapter
Colon Cancer Prevention

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 470))

Abstract

Elucidating the pathogenesis of colon cancer, one of the commonest fatal malignancies in the Western world, represents an important challenge for biomedical science. The seminal observation that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of and mortality from colorectal cancer1 has ushered in a new approach to the study of colon cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Thun, M.J., Namboodiri, M.M., and Heath C., Jr. Aspirin use and reduced risk of fatal colon cancer. New Engl. J. Med. 325:1593–1596, 1991.

    Article  PubMed  CAS  Google Scholar 

  2. Smith, W.L., Garavito, R.M., and De Witt, D.L. Prostaglandin endoperoxide H synthases (cyclooxygenases)-l and-2. J. Biol. Chemi. 271:33157–33160, 1996.

    Article  CAS  Google Scholar 

  3. Levy, G.N. Prostaglandin H synthases, nonsteroidal anti-inflammatory drugs, and colon cancer. FASEB J. 11:234–247, 1997.

    PubMed  CAS  Google Scholar 

  4. Kutchera, W., Jones, D.A., Matsunami, N., et al. Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect. Proc. Natl. Acad. Sci. USA 93:4816–4820, 1996.

    Article  PubMed  CAS  Google Scholar 

  5. Eberhart, C.E., Coffey, R.J., Radhika, A., Giardiello, F.M., Ferrenbach, S., and Dubois, R.N. Upregulation of cyclooxygenase 2 gene expression in human colorectal adenomas and carcinomas. Gastroenterol. 107:1183–1188, 1994.

    CAS  Google Scholar 

  6. Abramson, S.B. and Weissmann, G. The mechanisms of action of nonsteroidal antiinflammatory drugs. Arthritis Rheum. 32:1–9, 1989.

    Article  PubMed  CAS  Google Scholar 

  7. Pines, J. Cyclins, CDKs, and cancer. Semin. Cancer Biol. 6:63–72, 1995.

    Article  PubMed  CAS  Google Scholar 

  8. Bayer, B., Kruth, H., Vaughn, M., and Beaven, M. Arrest of cultured cells in the G1 phase of the cell cycle by indomethacin. J. Pharmacol. Exp. Therap. 210:106–111, 1979.

    CAS  Google Scholar 

  9. Bayer, G. and Beaven, M. Evidence that indomethacin reversibly inhibits cell growth in the G1 phase of the cell cycle. Biochem. Pharmacol. 28:441–443, 1979.

    Article  PubMed  CAS  Google Scholar 

  10. Shiff, S.J., Tsai, L., Qiao, L., and Rigas, B. The effect of sulindac on cell proliferation and the cell cycle distribution of human colon cancer cells. Gastroenterol. 106:A440, 1994.

    Google Scholar 

  11. Shiff, S.J., Qiao, L., Tsai, L.-L., and Rigas, B. Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells. J. Clin. Invest. 96:491–503, 1995.

    Article  PubMed  CAS  Google Scholar 

  12. Shiff, S.J., Koutsos, M.I., Qiao, L., and Rigas, B. Nonsteroidal antiinflammatory drugs inhibit the proliferation of colon adenocarcinoma cells: effects on cell cycle and apoptosis. Exp. Cell Res. 222:179–188, 1996.

    Article  PubMed  CAS  Google Scholar 

  13. Piazza, G.A., Rahm, A.L.K., Krutzsch, M., et al. Antineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis. Cancer Res. 55:3110–3116, 1995.

    PubMed  CAS  Google Scholar 

  14. Morgan, D.O. Principles of CDK regulation. Nature 374:131–134, 1995.

    Article  PubMed  CAS  Google Scholar 

  15. Sherr, C.J. Mammalian G1 cyclins. Cell 73:1059–1065, 1993.

    Article  PubMed  CAS  Google Scholar 

  16. Sherr, C.J. G1 phase progression: cycling on cue. Cell 79:551–555, 1994.

    Article  PubMed  CAS  Google Scholar 

  17. Maity, A., McKenna, W.G., and Muschel, R.J. The molecular basis for cell cycle delays following ionizing radiation: a review. Radiother. Oncol. 31:1–13, 1994.

    Article  PubMed  CAS  Google Scholar 

  18. Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B., and Craig, RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51:6304–6311, 1991.

    PubMed  CAS  Google Scholar 

  19. Shaw, P., Bovey, R., Tardy, S., Sahli, R., Sordat, B., and Costa, J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc. Natl. Acad. Sci. USA 89:4495–4499, 1992.

    Article  PubMed  CAS  Google Scholar 

  20. Fritsche, M., Haessler, C., and Brandner, G. Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 8:307–318, 1993.

    PubMed  CAS  Google Scholar 

  21. Leach, S.D., Scatena, C.D., Keefer, C.J., et al. Negative regulation of Weel expression and Cdc2 phosphorylation during p53-mediated growth arrest and apoptosis. Cancer Res. 58:3231–3236, 1998.

    PubMed  CAS  Google Scholar 

  22. Winters, Z.E., Ongkeko, W.M., Harris, A.L., and Norbury, C.J. p53 regulates Cdc2 independently of inhibitory phosphorylation to reinforce radiation-induced G2 arrest in human cells. Oncogene 17:673–684, 1998.

    Article  PubMed  CAS  Google Scholar 

  23. Weinberg, R.A. The retinoblastoma protein and cell cycle control. Cell 81:323–330, 1995.

    Article  PubMed  CAS  Google Scholar 

  24. Waddell, W.R. and Loughry, R.W Sulindac for polyposis of the colon. J. Surg. Oncol 24:83–87, 1983.

    Article  PubMed  CAS  Google Scholar 

  25. Giardiello, F.M., Hamilton, S.R., Krush, A.J., et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. New Engl. J. Med. 328:1313–1316, 1993.

    Article  PubMed  CAS  Google Scholar 

  26. Takayama, T., Katsuki, S., Takahashi, Y., et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer. New Engl. J. Med. 339:1277–1284, 1998.

    Article  PubMed  CAS  Google Scholar 

  27. Goldberg, Y., Nassif, I.I., Pittas, A., et al. The anti-proliferative effect of sulindac and sulindac sulfide on HT-29 colon cancer cells: Alterations in tumor suppressor and cell cycle-regulatory proteins. Oncogene 12:893–901, 1996.

    PubMed  CAS  Google Scholar 

  28. Qiao, L., Shiff, S.J., and Rigas, B. Sulindac sulfide alters the expression of cyclin proteins in HT-29 colon adenocarcinoma cells. Int. J. Cancer 76:99–104, 1998.

    Article  PubMed  CAS  Google Scholar 

  29. Qiao, L., Shiff, S.J., and Rigas, B. Sulindac sulfide induces several subpopulations of colon cancer cells, defined by PCNA/Ki-67 and DNA strand breaks. Biochim. Biophys. Acta 1359:222–232, 1997.

    Article  PubMed  CAS  Google Scholar 

  30. Qiao, L., Shiff, S.J., and Rigas, B. Sulindac sulfide inhibits the proliferation of colon cancer cells—diminished expression of the proliferation markers PCNA and Ki-67. Cancer Lett. 115:229–234, 1997.

    Article  PubMed  CAS  Google Scholar 

  31. Herrmann, C., Block, C., Geisen, C., et al. Sulindac sulfide inhibits Ras signaling. Oncogene 17:1769–1776, 1998.

    Article  PubMed  CAS  Google Scholar 

  32. Bos, J.L. Ras-like GTPases. Biochim. Biophys. Acta 1333:M19–31, 1997.

    PubMed  CAS  Google Scholar 

  33. Wang, A., Yoshimi, N., Suzui, M., Yamauchi, A., Tarao, M., and Mori, H. Different expression patterns of cyclins A, D1, and E in human colorectal cancer. J. Cancer Res. Clin. Oncol. 122:122–126, 1996.

    Article  PubMed  CAS  Google Scholar 

  34. Kitahara, K., Yasui, W., Kuniyasu, H., et al. Concurrent amplification of cyclin E and cdk2 genes in colorectal carcinomas. Int. J. Cancer 62:25–28, 1995.

    Article  PubMed  CAS  Google Scholar 

  35. Arber, R, Hibshoosh, H., Moss, S.F., et al. Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis. Gastroenterol. 110:669–674, 1996.

    Article  CAS  Google Scholar 

  36. DuBois, R.N., Shao, J., Tsujii, M., Sheng, H., and Beauchamp, R.D. G1 delay in cells overexpressing prostaglandin endoperoxide synthase-2. Cancer Res. 56:733–737, 1996.

    PubMed  CAS  Google Scholar 

  37. Hanif, R., Pittas, A., Feng, Y., et al. Effects of nonsteroidal antiinflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway. Biochem. Pharmacol. 52:237–245, 1996.

    Article  PubMed  CAS  Google Scholar 

  38. Elder, D.J.E., Hague, A., Hicks, D.J., and Paraskeva, C. Differential growth inhibition by the aspirin metabolite salicylate in human colorectal tumor cell lines: enhanced apoptosis in carcinoma and in vitro-transformed adenoma relative to adenoma cell lines. Cancer Res. 56:2273–2276, 1996.

    CAS  Google Scholar 

  39. Rigas, B. and Shiff, S.J. Is inhibition of cyclooxygenase required for the chemopreventive effect of NSAIDs in colon cancer? A model reconciling the current contradiction. Med. Hypotheses submitted.

    Google Scholar 

  40. Rodrigues, N.R., Rowan, A., Smith, M.E., et al. p53 mutations in colorectal cancer. Proc. Natl. Acad. Sci. USA 87:7555–7559, 1990.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rigas, B., Shiff, S.J. (1999). Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Cyclooxygenases, and the Cell Cycle. In: Colon Cancer Prevention. Advances in Experimental Medicine and Biology, vol 470. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4149-3_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4149-3_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6861-8

  • Online ISBN: 978-1-4615-4149-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics