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

doi:10.1038/sj.neo.7900177

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 journal › Article › peer-review

35 Scopus citations

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 G₂/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 G₂/M phase of the cell cycle.

Original language	English (US)
Pages (from-to)	428-436
Number of pages	9
Journal	Neoplasia
Volume	3
Issue number	5
DOIs	https://doi.org/10.1038/sj.neo.7900177
State	Published - 2001
Externally published	Yes

Keywords

COX-2
Cancer prevention
Cell cycle arrest
Colorectal cancer
Prostaglandins

ASJC Scopus subject areas

Cancer Research

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10.1038/sj.neo.7900177

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@article{0d1dc6e5780e42e4a93d27a5e770bcac,

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

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 G2/M transition. Accordingly, p34cdc2 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 G2/M phase of the cell cycle.",

keywords = "COX-2, Cancer prevention, Cell cycle arrest, Colorectal cancer, Prostaglandins",

author = "Williams, {Christopher S.} and Sheng Hongmiao and Brockman, {Jeffrey A.} and Radhika Armandla and Jinyi Shao and Washington, {M. Kay} and Elkahloun, {Abdel G.} and Dubois, {Raymond N.}",

note = "Funding Information: Address all correspondence to: Raymond N. Dubois, MD, PhD, Department of Medicine / GI, MCN C-2104, Vanderbilt University Medical Center, Nashville, TN 37232-2279. E-mail: raymond.dubois@mcmail.vanderbilt.edu 1This work was supported, in part, by the United States Public Health Services grants DK 47297 ( R. N. D. ), P030 ES -00267 - 29, DK48831, GM15431 (J. D. M.), P01 CA77839 - 01 and CA68485. R.N.D. is a recipient of a V.A. Research Merit Grant and the Mina C. Wallace Professor of Gastroenterology and Cancer Prevention. Received 18 March 2001; Accepted 9 May 2001.",

year = "2001",

doi = "10.1038/sj.neo.7900177",

language = "English (US)",

volume = "3",

pages = "428--436",

journal = "Neoplasia",

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T1 - A cyclooxygenase-2 inhibitor (SC-58125) blocks growth of established human colon cancer xenografts

AU - Williams, Christopher S.

AU - Hongmiao, Sheng

AU - Brockman, Jeffrey A.

AU - Armandla, Radhika

AU - Shao, Jinyi

AU - Washington, M. Kay

AU - Elkahloun, Abdel G.

AU - Dubois, Raymond N.

N1 - Funding Information: Address all correspondence to: Raymond N. Dubois, MD, PhD, Department of Medicine / GI, MCN C-2104, Vanderbilt University Medical Center, Nashville, TN 37232-2279. E-mail: raymond.dubois@mcmail.vanderbilt.edu 1This work was supported, in part, by the United States Public Health Services grants DK 47297 ( R. N. D. ), P030 ES -00267 - 29, DK48831, GM15431 (J. D. M.), P01 CA77839 - 01 and CA68485. R.N.D. is a recipient of a V.A. Research Merit Grant and the Mina C. Wallace Professor of Gastroenterology and Cancer Prevention. Received 18 March 2001; Accepted 9 May 2001.

PY - 2001

Y1 - 2001

N2 - 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 G2/M transition. Accordingly, p34cdc2 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 G2/M phase of the cell cycle.

AB - 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 G2/M transition. Accordingly, p34cdc2 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 G2/M phase of the cell cycle.

KW - COX-2

KW - Cancer prevention

KW - Cell cycle arrest

KW - Colorectal cancer

KW - Prostaglandins

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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