Clinical and genomic influence of sulindac on rectal mucosa in familial adenomatous polyposis

Abstract

Low-dose antiproliferative sulindac therapy is highly effective in adenoma reversion in familial adenomatous polyposis patients. Sulindac shows influence on tumor-suppressor genes and on apoptosis markers. An immunostaining correlation indicates adenoma relapse in flat microadenomas in advance of macroscopic appearance. Low-dose sulindac treatment may develop into an additive permnanent therapy for colectomized familial adenomatous polyposis patients.

Chemoprevention of intestinal tumorigenesis by nabumetone: induction of apoptosis and Bcl-2 downregulation

“…Furthermore, we demonstrate that nabumetone downregulation of Bcl-2 in HT-29 cells mirrored induction of apoptosis. Our data is in agreement with the demonstration that sulindac reduced Bcl-2 expression in both the uninvolved rectal mucosa of patients with FAP (Winde et al, 1997) and in MIN mouse adenomas (McEntee et al, 1999). The mechanism by which NSAIDS downregulate Bcl-2 is unclear, with one report implicating prostaglandin E2, (Sheng et al, 1998) although several lines of evidence suggesting that prostaglandin inhibition may not be essential for either NSAIDinduced apoptosis or chemoprevention (Williams et al, 1997).…”

Potency of non-steroidal anti-inflammatory drugs in chemotherapy

“…NSAIDs have been shown to inhibit malignant transformation in several cancer cell lines. Moreover, the frequent use of NSAIDs has been associated with a reduced risk of colorectal, gastrointestinal, breast, prostate and lung cancer (3)(4)(5)(6). The mechanism underlying the antitumour activity of NSAIDs has not been fully elucidated; however, it may involve the inhibition of COXs or other non-COX enzymatic pathways.…”

Sulindac targets nuclear β-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines

“…. Also, in patients with familial adenomatous polyposis (FAP), an autosomal dominantly inherited disorder characterised by the development of numerous colorectal adenomas at a young age, the NSAIDs sulindac and indomethacin can cause regression of adenomas (Giardiello et al, 1993;Nugent et al, 1993;Spagnesi et al, 1994;Hirota et al, 1996;Winde et al, 1997;Picariello et al, 1998). The chemopreventive effect of NSAIDs appears mediated by the induction of apoptosis and cell cycle arrest (Pasricha et al, 1995;DuBois and Smalley, 1996;Piazza et al, 1997;Keller et al, 1999;Shiff and Rigas, 1999).…”