Effect of Sulindac Sulfide on Metallohydrolases in the Human Colon Cancer Cell Line HT-29
نویسندگان
چکیده
Matrix metalloproteinase 7 (MMP7), a metallohydrolase involved in the development of several cancers, is downregulated in the Apc(Min/+) colon cancer mouse model following sulindac treatment. To determine whether this effect is relevant to the human condition, HT-29 human colon cancer cells were treated with sulindac and its metabolites, and compared to results obtained from in vivo mouse studies. The expression of MMP7 was monitored. The results demonstrated that sulindac sulfide effectively downregulated both MMP7 expression and activity. Furthermore, activity-based proteomics demonstrated that sulindac sulfide dramatically decreased the activity of leukotriene A4 hydrolase in HT-29 cells as reflected by a decrease in the level of its product, leukotriene B4. This study demonstrates that the effect of sulindac treatment in a mouse model of colon cancer may be relevant to the human counterpart and highlights the effect of sulindac treatment on metallohydrolases.
منابع مشابه
Evaluation of Radiosensitive Effect of Tolmetin in Radiotherapy on Human Colonic Carcinoma Cell Line HT-29
Background: Radiotherapy is one of the cancer treatment methods. Although radioresistance and normal tissue toxicity limit the radiation therapy in certain anatomical locations, using some substances can be useful to increase radiosensitivity on cancer cells without cytotoxicity effect on normal cells. Objective: This study aimed to evaluate the radiosensitizing effect of tolmetin in radiother...
متن کاملAntineoplastic drugs sulindac sulfide and sulfone inhibit cell growth by inducing apoptosis.
The nonsteroidal anti-inflammatory drug sulindac is known to inhibit chemical carcinogenesis in rodent models and cause regression of adenomas in patients with adenomatous polyposis coli. Sulindac is a prodrug that is metabolized to a pharmacologically active sulfide derivative that potently inhibits prostaglandin synthesis. Recent studies, however, have shown that a sulfone derivative of sulin...
متن کاملAntiproliferative effect of nonsteroidal antiinflammatory drugs against human colon cancer cells.
Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs...
متن کاملCompare the effect of ginger extract and aspirin on COX-2 gene expression in colon cancer cell line HT-29
Background and aim: Colon cancer is the third most prevalent cancer in Iran. Prolonged colon inflammation is an important factor, in the development of colon cancer. Ginger has anti-inflammatory properties due to its content of [6]-gingerol and hence can play a role in the prevention of colon cancer. In this research the effects of ginger extract on reducing expression of the C...
متن کاملEffects of nonsteroidal anti-inflammatory drugs on proliferation and on induction of apoptosis in colon cancer cells by a prostaglandin-independent pathway.
Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of and mortality from colon cancer. We observed that NSAIDs inhibit the proliferation rate, alter the cell cycle distribution, and induce apoptosis in colon cancer cell lines. We evaluated whether the inhibition by NSAIDs of prostaglandin (PG) synthesis is required for their effects on colon cancer cells by studying two human ...
متن کامل