Cyclooxygenase-Independent Induction of P2LWAF-1/CIP1, Apoptosis and Differentiation by L-745, 337 and Salicylate in HT-29 Colon Cancer Cells

Patrignani, Paola; Santini, Giovanna; Sciulli, Maria G.; Marinacci, R.; Fusco, O.; Spoletini, L; Natoli, Clara; Procopio, Antonio; Maclouf, Jacques

doi:10.1007/978-1-4615-4793-8_81

Cited by 4 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies show that sulindac sulfide inhibits COX activity, but not the sulfone metabolite (44), and both sulindac sulfide and sulfone are reported to induce apoptosis in different cell types (44)(45)(46). Many COX-2independent mechanisms have been investigated which mediate inhibition of tumors with NSAIDs (47)(48)(49)(50)(51)(52).…”

Section: Discussionmentioning

confidence: 99%

Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations

et al. 2003

View full text Add to dashboard Cite

Sulindac and other NSAIDs have been widely studied as potential chemopreventive agents for colon cancer. Short-term studies have shown adenomatous polyps to regress in patients with familial adenomatous polyposis (FAP). In this study the effect of sulindac on cancer as an endpoint was evaluated in ApcMin mice, a preclinical model of FAP with an Apc mutation in codon 850 that leads to gastrointestinal adenomas and carcinomas. Three groups of mice were studied all of which were fed AIN-76A diet: one group was fed AIN-76A diet alone, a second group received sulindac 200 p.p.m. premixed in the diet and a third group received sulindac 180 p.p.m. added in drinking water. ApcMin mice were killed 9 weeks after feeding was initiated. Mice receiving sulindac developed fewer tumors in the intestine overall; the major decrease in tumor development after sulindac was seen in the small intestine regardless of route of administration. In the large intestine, however, sulindac significantly increased the incidence, multiplicity and volume of tumors in the colon of ApcMin mice, a regional response to sulindac differing from previous reports. Quantitative measurements of apoptosis, Bax and Bcl-xL protein expression in the ApcMin mice revealed the ratio of Bax/Bcl-xL expression and apoptosis increased in the small intestine but decreased in the cecum, consistent with the regional tumorigenesis observed after sulindac. These findings thus suggest involvement of Bax and apoptosis in tumors developing after sulindac treatment in this mouse model.

show abstract

Section: Discussionmentioning

confidence: 99%

Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations

et al. 2003

View full text Add to dashboard Cite

show abstract

The COX-2 Inhibitor NS-398 Causes T-Cell Developmental Disruptions Independent of COX-2 Enzyme Inhibition

Izon

Loftin

et al. 2001

Cellular Immunology

View full text Add to dashboard Cite

Inhibition of Human Glioma Cell Growth by a PHS-2 Inhibitor, NS398, and a Prostaglandin E Receptor Subtype EP1-selective Antagonist, SC51089

et al. 2004

View full text Add to dashboard Cite

Prostaglandin H synthase (PHS) is a key enzyme in the synthesis of prostaglandins (PGs). Recently, enhanced expression of PHS-2 in brain tumors and the correlation between the PHS-2 level and the histopathological grade of glioma has been reported. Furthermore, in vitro inhibition of glioma cell growth by a specific PHS-2 inhibitor, NS398, has been demonstrated. It has also been shown that prostaglandin E2 (PGE2) contributes to colon carcinogenesis by binding to the prostaglandin E receptor subtype EP1. We therefore evaluated the effects of NS398 and two EP1 antagonists, SC51089 and AH6809, on glioma cell lines. To evaluate mechanisms of NS398's action, two glioma cell lines, a PHS-2-positive cell line (KMG4) and a PHS-2-deficient cell line (A 172), were used. NS398 inhibited both the anchorage-dependent and -independent growth of glioma cell lines regardless of PHS-2 expression, suggesting that some PHS-2-independent mechanisms underlie the antineoplastic effect of NS398. However, the antineoplastic effect was attenuated by the addition of PGE2, which is one of the main products of PHS, suggesting the predominant mechanism is PHS-dependent. The EP1 antagonists, SC51089 and AH6809, inhibited the growth of glioma cell lines in vitro. Furthermore, NS398 or SC51089 slowed tumor growth in vivo, which was assessed using KMG4 tumor xenografts on SCID mice. PHS-2 inhibitors and EP1 antagonists might be useful in the prevention and/or treatment of glioma.

show abstract

Cyclooxygenase-Independent Induction of P2LWAF-1/CIP1, Apoptosis and Differentiation by L-745, 337 and Salicylate in HT-29 Colon Cancer Cells

Cited by 4 publications

References 14 publications

Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations

Regional response leading to tumorigenesis after sulindac in small and large intestine of mice with Apc mutations

The COX-2 Inhibitor NS-398 Causes T-Cell Developmental Disruptions Independent of COX-2 Enzyme Inhibition

Inhibition of Human Glioma Cell Growth by a PHS-2 Inhibitor, NS398, and a Prostaglandin E Receptor Subtype EP1-selective Antagonist, SC51089

Contact Info

Product

Resources

About