PMID: 9192825Jun 15, 1997Paper

Apoptosis primarily accounts for the growth-inhibitory properties of sulindac metabolites and involves a mechanism that is independent of cyclooxygenase inhibition, cell cycle arrest, and p53 induction

Cancer Research
G A PiazzaD J Ahnen

Abstract

Sulindac causes regression of and prevents recurrence of colonic adenomas in patients with familial adenomatous polyposis. Although cell cycle arrest and apoptosis have been proposed, the mechanism of action is poorly understood. In this study, we characterized the growth-inhibitory effects of active metabolites of sulindac in cultured colon adenocarcinoma cells by determining the contribution of apoptosis and cell cycle arrest and the requirement for cyclooxygenase (COX) inhibition and p53 involvement and compared the effects of sulindac metabolites with the chemotherapeutic drug, 5-fluorouracil (5-FU). Time course and dose-response experiments demonstrated that increased apoptosis paralleled the growth-inhibitory effects of the sulfide and sulfone. A relationship among a series of nonsteroidal anti-inflammatory drugs was observed between potency for growth inhibition and ability to induce apoptosis but not potency to inhibit COX. For example, the sulfone was at least 5000-fold less potent than the sulfide for inhibiting COX but only 6.5-fold less potent for inducing apoptosis. Moreover, the prostaglandin analogue, dimethyl-prostaglandin E2, failed to reverse the apoptosis-inducing effects of the sulfide. Sulindac metabolites ...Continue Reading

Related Concepts

Related Feeds

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis