The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis

Pankaj Jay Pasricha, Atul Bedi, Kathryn O'Connor, Asif Rashid, Adil J. Akhtar, Marianna L. Zahurak, Steven Piantadosi, Stanley R. Hamilton, Francis M Giardiello

Research output: Contribution to journalArticle

Abstract

Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. Methods: Cell proliferation was studied via immunohistochemistry for proliferating cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. Results: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% ± 4.8% compared with 10% ± 4.3% at baseline; P = 0.01). Conclusions: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

Original languageEnglish (US)
Pages (from-to)994-998
Number of pages5
JournalGastroenterology
Volume109
Issue number3
DOIs
StatePublished - 1995

Fingerprint

Sulindac
Adenomatous Polyposis Coli
Apoptosis
Cell Cycle
Proliferating Cell Nuclear Antigen
Polyps
Adenoma
Flow Cytometry
Cell Death
Epithelium
Epithelial Cells
Immunohistochemistry
Placebos
Cell Proliferation
Therapeutics

ASJC Scopus subject areas

  • Gastroenterology

Cite this

The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis. / Pasricha, Pankaj Jay; Bedi, Atul; O'Connor, Kathryn; Rashid, Asif; Akhtar, Adil J.; Zahurak, Marianna L.; Piantadosi, Steven; Hamilton, Stanley R.; Giardiello, Francis M.

In: Gastroenterology, Vol. 109, No. 3, 1995, p. 994-998.

Research output: Contribution to journalArticle

Pasricha, Pankaj Jay ; Bedi, Atul ; O'Connor, Kathryn ; Rashid, Asif ; Akhtar, Adil J. ; Zahurak, Marianna L. ; Piantadosi, Steven ; Hamilton, Stanley R. ; Giardiello, Francis M. / The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis. In: Gastroenterology. 1995 ; Vol. 109, No. 3. pp. 994-998.
@article{6ab60df19c9949afb38047b54a30c02e,
title = "The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis",
abstract = "Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. Methods: Cell proliferation was studied via immunohistochemistry for proliferating cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. Results: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3{\%} ± 4.8{\%} compared with 10{\%} ± 4.3{\%} at baseline; P = 0.01). Conclusions: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.",
author = "Pasricha, {Pankaj Jay} and Atul Bedi and Kathryn O'Connor and Asif Rashid and Akhtar, {Adil J.} and Zahurak, {Marianna L.} and Steven Piantadosi and Hamilton, {Stanley R.} and Giardiello, {Francis M}",
year = "1995",
doi = "10.1016/0016-5085(95)90411-5",
language = "English (US)",
volume = "109",
pages = "994--998",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

TY - JOUR

T1 - The effects of sulindac on colorectal proliferation and apoptosis in familial adenomatous polyposis

AU - Pasricha, Pankaj Jay

AU - Bedi, Atul

AU - O'Connor, Kathryn

AU - Rashid, Asif

AU - Akhtar, Adil J.

AU - Zahurak, Marianna L.

AU - Piantadosi, Steven

AU - Hamilton, Stanley R.

AU - Giardiello, Francis M

PY - 1995

Y1 - 1995

N2 - Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. Methods: Cell proliferation was studied via immunohistochemistry for proliferating cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. Results: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% ± 4.8% compared with 10% ± 4.3% at baseline; P = 0.01). Conclusions: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

AB - Background & Aims: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP. Methods: Cell proliferation was studied via immunohistochemistry for proliferating cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis. Results: Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% ± 4.8% compared with 10% ± 4.3% at baseline; P = 0.01). Conclusions: Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.

UR - http://www.scopus.com/inward/record.url?scp=0029088472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029088472&partnerID=8YFLogxK

U2 - 10.1016/0016-5085(95)90411-5

DO - 10.1016/0016-5085(95)90411-5

M3 - Article

C2 - 7657130

AN - SCOPUS:0029088472

VL - 109

SP - 994

EP - 998

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 3

ER -