A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts

Christopher S. Williams, Sheng Hongmiao, Jeffrey A. Brockman, Radhika Armandla, Jinyi Shao, M. Kay Washington, Abdel G. Elkahloun, Raymond N. Dubois

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Selective COX-2 inhibitors reduce adenoma formation and cancer progression in rodent models of colorectal cancer. To assess the therapeutic activity of selective COX-2 inhibitors, we tested the effect of SC-58125 treatment on the growth of human colon carcinoma cells in nude mice. Delaying treatment by 2, 4, or 7 weeks following implantation of the carcinoma cells resulted in a significant inhibition of tumor growth. Furthermore, short-term (48 hours) treatment with SC-58125 was sufficient to attenuate tumor growth for up to 15 days. SC-58125 treatment did not alter the rate at which cells underwent apoptosis, but did result in a delayed progression through the cell cycle at the G 2/M transition. Accordingly, p34 cdc2 protein levels and activity were decreased following SC-58125 treatment. We conclude that SC-58125 primarily exerts a cytostatic effect in vivo, which is likely to be mediated through inhibition of progression through the G 2/M phase of the cell cycle.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalNeoplasia
Volume3
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Cyclooxygenase 2 Inhibitors
Heterografts
Colonic Neoplasms
Growth
Cell Cycle
CDC2 Protein Kinase
Carcinoma
Neoplasms
Cytostatic Agents
Nude Mice
Cell Division
Adenoma
Colorectal Neoplasms
Rodentia
Colon
1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
Apoptosis

Keywords

  • Cancer prevention
  • Cell cycle arrest
  • Colorectal cancer
  • COX-2
  • Prostaglandins

ASJC Scopus subject areas

  • Cancer Research

Cite this

Williams, C. S., Hongmiao, S., Brockman, J. A., Armandla, R., Shao, J., Washington, M. K., ... Dubois, R. N. (2001). A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia, 3(5), 428-436. https://doi.org/10.1038/sj.neo.7900177

A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. / Williams, Christopher S.; Hongmiao, Sheng; Brockman, Jeffrey A.; Armandla, Radhika; Shao, Jinyi; Washington, M. Kay; Elkahloun, Abdel G.; Dubois, Raymond N.

In: Neoplasia, Vol. 3, No. 5, 2001, p. 428-436.

Research output: Contribution to journalArticle

Williams, CS, Hongmiao, S, Brockman, JA, Armandla, R, Shao, J, Washington, MK, Elkahloun, AG & Dubois, RN 2001, 'A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts', Neoplasia, vol. 3, no. 5, pp. 428-436. https://doi.org/10.1038/sj.neo.7900177
Williams CS, Hongmiao S, Brockman JA, Armandla R, Shao J, Washington MK et al. A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. Neoplasia. 2001;3(5):428-436. https://doi.org/10.1038/sj.neo.7900177
Williams, Christopher S. ; Hongmiao, Sheng ; Brockman, Jeffrey A. ; Armandla, Radhika ; Shao, Jinyi ; Washington, M. Kay ; Elkahloun, Abdel G. ; Dubois, Raymond N. / A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts. In: Neoplasia. 2001 ; Vol. 3, No. 5. pp. 428-436.
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