Rice, Pamela L. published the artcileSulindac metabolites induce caspase- and proteasome-dependent degradation of β-catenin protein in human colon cancer cells, Formula: C20H17FO4S, the publication is Molecular Cancer Therapeutics (2003), 2(9), 885-892, database is CAplus.
Colorectal cancer (CRC) is the second leading cause of cancer death in the USA. Accumulation of β-catenin protein is nearly ubiquitous in colon adenomas and cancers, presumably due to mutations in the APC or β-catenin genes that inhibit proteasome-dependent degradation of β-catenin protein. Substantial clin., epidemiol., and animal evidence indicate that sulindac and other non-steroidal anti-inflammatory drugs (NSAIDs) prevent the development of CRC. The mechanisms by which sulindac exerts its potent growth inhibitory effects against colon tumor cells are incompletely understood, but down-regulation of β-catenin was suggested as one potential mechanism. The goal of this study was to determine the mechanism of β-catenin protein down-regulation by sulindac metabolites. Treatment of human colon cancer cell lines with apoptotic concentrations of sulindac metabolites (sulindac sulfide, sulindac sulfone) induced a dose- and time-dependent inhibition of β-catenin protein expression. Inhibition of proteasome activity with MG-132 partially blocked the ability of sulindac sulfide and sulindac sulfone to inhibit β-catenin protein expression. Pretreatment with the caspase inhibitor z-VAD-fmk blocked morphol. signs of apoptosis as well as caspase cleavage, and also partially prevented β-catenin degradation by sulindac metabolites. These effects occurred in cells with bi-allelic APC mutation (SW480), with wild-type APC but mono-allelic β-catenin mutation (HCT116) and in cells that lack expression of either COX-1 or -2 (HCT15). These results indicate that loss of β-catenin protein induced by sulindac metabolites is COX independent and at least partially due to reactivation of β-catenin proteasome degradation and partially a result of caspase activation during the process of apoptosis.
Molecular Cancer Therapeutics published new progress about 59973-80-7. 59973-80-7 belongs to naphthyridine, auxiliary class Immunology/Inflammation,COX, name is Sulindac sulfone, and the molecular formula is C20H17FO4S, Formula: C20H17FO4S.
Referemce:
https://en.wikipedia.org/wiki/1,8-Naphthyridine,
1,8-Naphthyridine | C8H6N2 – PubChem