sulindac

Summary

Summary: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.

Top Publications

  1. Tinsley H, Gary B, Keeton A, Lu W, Li Y, Piazza G. Inhibition of PDE5 by sulindac sulfide selectively induces apoptosis and attenuates oncogenic Wnt/?-catenin-mediated transcription in human breast tumor cells. Cancer Prev Res (Phila). 2011;4:1275-84 pubmed publisher
    Nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide (SS) display promising antineoplastic properties, but toxicities resulting from COX inhibition limit their clinical use...
  2. Resnick L, Rabinovitz H, BINNINGER D, Marchetti M, Weissbach H. Topical sulindac combined with hydrogen peroxide in the treatment of actinic keratoses. J Drugs Dermatol. 2009;8:29-32 pubmed
    ..b>Sulindac is a Food and Drug Administration (FDA)-approved nonsteroidal anti-inflammatory drug (NSAID) that has been shown ..
  3. Jin H, Seo S, Woo S, Lee H, Kim E, Yoo D, et al. A combination of sulindac and arsenic trioxide synergistically induces apoptosis in human lung cancer H1299 cells via c-Jun NH2-terminal kinase-dependent Bcl-xL phosphorylation. Lung Cancer. 2008;61:317-27 pubmed publisher
    In the present study, we show that a combination of sulindac and arsenic trioxide (ATO) induces more extensive apoptosis than either drug alone in H1299 human non-small cell lung carcinoma (NSCLC) cells...
  4. Chiou S, Hodges A, Hoa N. Suppression of growth arrest and DNA damage-inducible 45alpha expression confers resistance to sulindac and indomethacin-induced gastric mucosal injury. J Pharmacol Exp Ther. 2010;334:693-702 pubmed publisher
    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac and indomethacin are a major cause of gastric erosions and ulcers. Induction of apoptosis by NSAIDs is an important mechanism involved...
  5. Limburg P, Mahoney M, Ziegler K, Sontag S, Schoen R, BENYA R, et al. Randomized phase II trial of sulindac, atorvastatin, and prebiotic dietary fiber for colorectal cancer chemoprevention. Cancer Prev Res (Phila). 2011;4:259-69 pubmed publisher
    b>Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited...
  6. Skopinski P, Szaflik J, Duda Król B, Nartowska J, Sommer E, Chorostowska Wynimko J, et al. Suppression of angiogenic activity of sera from diabetic patients with non-proliferative retinopathy by compounds of herbal origin and sulindac sulfone. Int J Mol Med. 2004;14:707-11 pubmed
    ..The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice...
  7. Li H, Pamukcu R, Thompson W. beta-Catenin signaling: therapeutic strategies in oncology. Cancer Biol Ther. 2002;1:621-5 pubmed
    ..Since this pathway is independent of APC and GSK3beta, exisulind and analogs provide a superior approach to circumvent the molecular defects of wnt signaling pathway and to treat cancers with such defects. ..
  8. Minagawa K, Berber M, Hafez I, Mori T, Tanaka M. Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system. J Mater Sci Mater Med. 2012;23:973-81 pubmed publisher
    Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry...
  9. Moschos C, Psallidas I, Cottin T, Kollintza A, Papiris S, Roussos C, et al. A sulindac analogue is effective against malignant pleural effusion in mice. Lung Cancer. 2011;73:171-5 pubmed publisher
    To examine whether a sulindac derivative (C-18) with previously reported anti-angiogenic properties limits malignant pleural effusion (MPE) formation in mice...

More Information

Publications95

  1. Ciolino H, Bass S, MacDonald C, Cheng R, Yeh G. Sulindac and its metabolites induce carcinogen metabolizing enzymes in human colon cancer cells. Int J Cancer. 2008;122:990-8 pubmed
    b>Sulindac is a nonsteroidal antiinflammatory drug that has been demonstrated to be a potent chemopreventive agent against colorectal cancer in both human and animal models...
  2. Tinsley H, Gary B, Keeton A, Zhang W, Abadi A, Reynolds R, et al. Sulindac sulfide selectively inhibits growth and induces apoptosis of human breast tumor cells by phosphodiesterase 5 inhibition, elevation of cyclic GMP, and activation of protein kinase G. Mol Cancer Ther. 2009;8:3331-40 pubmed publisher
    b>Sulindac displays promising antineoplastic activity, but toxicities from cyclooxygenase inhibition limit its use for chemoprevention...
  3. Lim J, Joe A, Suzui M, Shimizu M, Masuda M, Weinstein I. Sulindac sulfide and exisulind inhibit expression of the estrogen and progesterone receptors in human breast cancer cells. Clin Cancer Res. 2006;12:3478-84 pubmed
    In previous studies, we found that sulindac sulfide and exisulind (sulindac sulfone, Aptosyn) cause growth inhibition, arrest cells in the G1 phase of the cell cycle, and induce apoptosis in human breast cancer cell lines...
  4. Babbar N, Ignatenko N, Casero R, Gerner E. Cyclooxygenase-independent induction of apoptosis by sulindac sulfone is mediated by polyamines in colon cancer. J Biol Chem. 2003;278:47762-75 pubmed
    b>Sulindac, a non-steroidal anti-inflammatory prodrug, is metabolized into pharmacologically active sulfide and sulfone derivatives...
  5. Jang T, Jung K, Choi E. Id-1 gene downregulation by sulindac sulfide and its upregulation during tumor development in gastric cancer. Int J Cancer. 2006;118:1356-63 pubmed
    ..We examined gene expression profiles in SNU601 gastric cancer cells treated with sulindac sulfide (50 microM) for 24 hr. Microarray analysis showed that 1...
  6. Stein U, Arlt F, Smith J, Sack U, Herrmann P, Walther W, et al. Intervening in ?-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia. 2011;13:131-44 pubmed
    ..Here we probe the hypothesis that the nonsteroidal anti-inflammatory drug sulindac sulfide can inhibit colon cancer metastasis by intervening in ?-catenin signaling and thereby interdicting S100A4...
  7. Zhou H, Liu W, Su Y, Wei Z, Liu J, Kolluri S, et al. NSAID sulindac and its analog bind RXRalpha and inhibit RXRalpha-dependent AKT signaling. Cancer Cell. 2010;17:560-73 pubmed publisher
    ..Here, we report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-alpha (RXRalpha)...
  8. Jones S, Kuhn J, Greco F, Raefsky E, Hainsworth J, Dickson N, et al. A phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer. Clin Lung Cancer. 2005;6:361-6 pubmed
    Exisulind is a sulfone derivative of sulindac that induces apoptosis and demonstrates synergy with docetaxel in lung cancer models...
  9. Pyriochou A, Tsigkos S, Vassilakopoulos T, Cottin T, Zhou Z, Gourzoulidou E, et al. Anti-angiogenic properties of a sulindac analogue. Br J Pharmacol. 2007;152:1207-14 pubmed
    ..We have recently described a sulindac analogue 2-((1E,Z)-1-benzylidene-5-bromo-2-methyl-1H-inden-3-yl)acetic acid; termed C-18 from now onwards) that ..
  10. Yang W, Bancroft L, Liang J, Zhuang M, Augenlicht L. p27kip1 in intestinal tumorigenesis and chemoprevention in the mouse. Cancer Res. 2005;65:9363-8 pubmed
    ..of another cyclin-dependent kinase inhibitor, p21(WAF1/cip1), the nonsteroidal anti-inflammatory drug sulindac was still effective in inhibiting intestinal tumor formation in Apc(+/-),p27(+/-) or Apc(+/-),p27(-/-) mice, ..
  11. Zell J, McLaren C, Chen W, Thompson P, Gerner E, Meyskens F. Ornithine decarboxylase-1 polymorphism, chemoprevention with eflornithine and sulindac, and outcomes among colorectal adenoma patients. J Natl Cancer Inst. 2010;102:1513-6 pubmed publisher
    ..We investigated the effects of ODC1 after treatment with difluoromethylornithine (eflornithine)/sulindac or placebo...
  12. Hwang K, Park C, Kwon S, Kim Y, Park D, Lee M, et al. Synergistic induction of apoptosis by sulindac and simvastatin in A549 human lung cancer cells via reactive oxygen species-dependent mitochondrial dysfunction. Int J Oncol. 2013;43:262-70 pubmed publisher
    ..This study was designed to investigate lung cancer chemoprevention through a mechanism-based approach using sulindac at low doses in combination with simvastatin...
  13. Huang Y, He Q, Hillman M, Rong R, Sheikh M. Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells. Cancer Res. 2001;61:6918-24 pubmed
    b>Sulindac is the most extensively investigated clinically relevant chemopreventive nonsteroidal anti-inflammatory drug...
  14. McLaren C, Fujikawa Brooks S, Chen W, Gillen D, Pelot D, Gerner E, et al. Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila). 2008;1:514-21 pubmed publisher
    ..the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos...
  15. Wong C, Cheng K, Xie G, Zhou D, Zhu C, Constantinides P, et al. Carboxylesterases 1 and 2 hydrolyze phospho-nonsteroidal anti-inflammatory drugs: relevance to their pharmacological activity. J Pharmacol Exp Ther. 2012;340:422-32 pubmed publisher
    ..Kinetic analysis revealed that CES1 is more active in the hydrolysis of phospho-sulindac, phospho-ibuprofen, phospho-naproxen, phospho-indomethacin, and phospho-tyrosol-indomethacin that possessed a ..
  16. Romeiro N, Leite R, Lima L, Cardozo S, de Miranda A, Fraga C, et al. Synthesis, pharmacological evaluation and docking studies of new sulindac analogues. Eur J Med Chem. 2009;44:1959-71 pubmed publisher
    This paper describes the synthesis, pharmacological evaluation and docking studies of a series of new sulindac analogues...
  17. Sinibaldi V, Elza Brown K, Schmidt J, Eisenberger M, Rosenbaum E, Denmeade S, et al. Phase II evaluation of docetaxel plus exisulind in patients with androgen independent prostate carcinoma. Am J Clin Oncol. 2006;29:395-8 pubmed
    ..Overall, our trial indicated that the toxicity profile and efficacy of this regimen is unlikely to be substantially better than single agent docetaxel. ..
  18. Seo A, Hong S, Shin J, Park I, Hong N, Kim D, et al. Sulindac induces apoptotic cell death in susceptible human breast cancer cells through, at least in part, inhibition of IKKbeta. Apoptosis. 2009;14:913-22 pubmed publisher
    b>Sulindac is a non-steroidal anti-inflammatory agent with anti-tumor activities that include the induction of apoptosis in various cancer cells and the inhibition malignant transformation...
  19. Li N, Xi Y, Tinsley H, Gurpinar E, Gary B, Zhu B, et al. Sulindac selectively inhibits colon tumor cell growth by activating the cGMP/PKG pathway to suppress Wnt/?-catenin signaling. Mol Cancer Ther. 2013;12:1848-59 pubmed publisher
    ..Here, we report that the NSAID sulindac sulfide inhibits cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE) activity to increase ..
  20. Dairam A, Antunes E, Saravanan K, Daya S. Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sci. 2006;79:2269-74 pubmed
    ..In this study, we determined the effect of the non-steroidal anti-inflammatory agents, tolmetin and sulindac, on rat liver TDO activity and the subsequent changes in the hippocampal and striatal neurotransmitter levels...
  21. Huang L, Zhu C, Sun Y, Xie G, MacKenzie G, Qiao G, et al. Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect. Carcinogenesis. 2010;31:1982-90 pubmed publisher
    Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy...
  22. Itano O, Yang K, Fan K, Kurihara N, Shinozaki H, Abe S, et al. Sulindac effects on inflammation and tumorigenesis in the intestine of mice with Apc and Mlh1 mutations. Carcinogenesis. 2009;30:1923-6 pubmed publisher
    We have previously reported that sulindac, a non-steroidal anti-inflammatory drug, inhibited tumor formation in the small intestine but increased tumors in the colon of Apc(Min/+) mice, a model of human familial adenomatous polyposis...
  23. Jiang T, Brown S, Kim J. Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro. J Exp Clin Cancer Res. 2004;23:259-62 pubmed
    ..In this study we tested sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID) to test its effects with arsenic...
  24. Kishimoto Y, Yashima K, Morisawa T, Ohishi T, Marumoto A, Sano A, et al. Effects of long-term administration of sulindac on APC mRNA and apoptosis in colons of rats treated with azoxymethane. J Cancer Res Clin Oncol. 2002;128:589-95 pubmed
    Non-steroidal anti-inflammatory drugs, including sulindac, have been shown to exhibit anti-colon cancer activity; however, the detailed mechanisms concerning continuous long-term administration are still unclear...
  25. Yip Schneider M, Nakshatri H, Sweeney C, Marshall M, Wiebke E, Schmidt C. Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells. Mol Cancer Ther. 2005;4:587-94 pubmed
    ..cells to NSAID inhibition, BxPC-3, PANC-1, and MIA PaCa-2 cells were treated with parthenolide and the NSAID sulindac, either alone or in combination...
  26. Mladenova D, Daniel J, Dahlstrom J, Bean E, Gupta R, Pickford R, et al. The NSAID sulindac is chemopreventive in the mouse distal colon but carcinogenic in the proximal colon. Gut. 2011;60:350-60 pubmed publisher
    The non-steroidal anti-inflammatory drug sulindac is an effective chemopreventive agent in sporadic colorectal cancer but its potential benefit in mismatch repair deficient cancers remains to be defined...
  27. Agarwal B, Swaroop P, Protiva P, Raj S, Shirin H, Holt P. Cox-2 is needed but not sufficient for apoptosis induced by Cox-2 selective inhibitors in colon cancer cells. Apoptosis. 2003;8:649-54 pubmed
    ..In contrast, sulindac sulfide (SSD) (which inhibits Cox-1 and Cox-2) 0-200 microM or sulindac sulfone (SSN) 0-500 microM (without ..
  28. Moon Y, Yang H, Kim Y. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells. Toxicol Appl Pharmacol. 2007;223:155-63 pubmed
    ..In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an ..
  29. Hoang T, Kim K, Merchant J, Traynor A, McGovern J, Oettel K, et al. Phase I/II study of gemcitabine and exisulind as second-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2006;1:218-25 pubmed
    ..1 months in phase II), we did not observe a clear survival advantage and thus do not plan to further investigate this schedule of gemcitabine and exisulind. ..
  30. Adachi M, Sakamoto H, Kawamura R, Wang W, Imai K, Shinomura Y. Nonsteroidal anti-inflammatory drugs and oxidative stress in cancer cells. Histol Histopathol. 2007;22:437-42 pubmed publisher
    ..In addition, the classical NSAIDs sulindac and aspirin are promising chemopreventive agents against colon cancer...
  31. Hu Y, Le Leu R, Young G. Defective acute apoptotic response to genotoxic carcinogen in small intestine of APC(Min/+) mice is restored by sulindac. Cancer Lett. 2007;248:234-44 pubmed
    ..effect of APC loss on azoxymethane (AOM)-induced apoptosis and cell proliferation, as well as their regulation by sulindac was examined in colon and small intestine in APC(Min/+) mice...
  32. Dairam A, Chetty P, Daya S. Non-steroidal anti-inflammatory agents, tolmetin and sulindac, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons. Metab Brain Dis. 2006;21:221-33 pubmed
    ..antioxidant and neuroprotective properties of two non-steroidal anti-inflammatory drugs (NSAIDS), tolmetin and sulindac, using quinolinic acid (QA)-induced neurotoxicity as a model...
  33. Chiou S, Hoa N, Hodges A. Sulindac sulfide induces autophagic death in gastric epithelial cells via survivin down-regulation: a mechanism of NSAIDs-induced gastric injury. Biochem Pharmacol. 2011;81:1317-23 pubmed publisher
    b>Sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID), has anti-tumorigenic and anti-inflammatory activities, but causes gastric mucosal damage...
  34. Kim H, Kim E, Yang S, Jeong E, Park C, Kim S, et al. Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction. Int J Oncol. 2006;28:1401-8 pubmed
    ..Herein, we demonstrate that the combination treatment of arsenic trioxide (As2O3) and sulindac resulted in a synergistic augmentation of cytotoxicity toward NCI-H157 lung cancer cells, which was revealed as ..
  35. O CONNOR R, O LEARY M, Ballot J, Collins C, Kinsella P, Mager D, et al. A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer. Cancer Chemother Pharmacol. 2007;59:79-87 pubmed
    ..b>Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug ..
  36. Walters M, Blobaum A, Kingsley P, Felts A, Sulikowski G, Marnett L. The influence of double bond geometry in the inhibition of cyclooxygenases by sulindac derivatives. Bioorg Med Chem Lett. 2009;19:3271-4 pubmed publisher
    b>Sulindac sulfide is a benzylidene-indene that is a potent, time-dependent inhibitor of cyclooxygenases-1 and -2...
  37. Moon Y, Kim J, Yang H, Eling T. Growth compensatory role of sulindac sulfide-induced thrombospondin-1 linked with ERK1/2 and RhoA GTPase signaling pathways. Life Sci. 2008;82:591-9 pubmed publisher
    ..Among diverse NSAIDs, sulindac sulfide was most potent of inducing the human TSP-1 protein expression...
  38. Seo S, Jin H, Lee H, Woo S, Kim E, Yoo D, et al. Combined effects of sulindac and suberoylanilide hydroxamic acid on apoptosis induction in human lung cancer cells. Mol Pharmacol. 2008;73:1005-12 pubmed
    ..In the present study, we show that at the suboptimal dose of 250 muM, sulindac [2-[6-fluoro-2-methyl-3-[(4-methylsulfinylphenyl)methylidene]inden-1-yl]-acetic acid] significantly enhances SAHA-..
  39. Hizawa K, Nakamori M, Yao T, Matsumoto T, Iida M. A case of Cronkhite-Canada syndrome with colorectal adenomas: effect of the nonsteroidal anti-inflammatory drug sulindac. Am J Gastroenterol. 2007;102:1831-2 pubmed
  40. Meyskens F, McLaren C, Pelot D, Fujikawa Brooks S, Carpenter P, Hawk E, et al. Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila). 2008;1:32-8 pubmed publisher
    ..gt; or =3 mm) adenomas were randomly assigned to receive oral difluoromethylornithine (DFMO) 500 mg and sulindac 150 mg once daily or matched placebos for 36 months, stratified by use of low-dose aspirin (81 mg) at baseline ..
  41. Kim S, Jang T, Jung K, Suh J. Sulindac prevents esophageal adenocarcinomas induced by gastroduodenal reflux in rats. Yonsei Med J. 2007;48:1020-7 pubmed
    ..We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal ..
  42. Xie G, Nie T, Mackenzie G, Sun Y, Huang L, Ouyang N, et al. The metabolism and pharmacokinetics of phospho-sulindac (OXT-328) and the effect of difluoromethylornithine. Br J Pharmacol. 2012;165:2152-66 pubmed publisher
    Phospho-sulindac (PS; OXT-328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics...
  43. Whitt J, Li N, Tinsley H, Chen X, Zhang W, Li Y, et al. A novel sulindac derivative that potently suppresses colon tumor cell growth by inhibiting cGMP phosphodiesterase and ?-catenin transcriptional activity. Cancer Prev Res (Phila). 2012;5:822-33 pubmed publisher
    ..Here, we characterize a novel sulindac derivative referred to as sulindac benzylamine (SBA) that does not inhibit COX-1 or COX-2, yet potently inhibits ..
  44. Zhu R, Cheng K, Mackenzie G, Huang L, Sun Y, Xie G, et al. Phospho-sulindac (OXT-328) inhibits the growth of human lung cancer xenografts in mice: enhanced efficacy and mitochondria targeting by its formulation in solid lipid nanoparticles. Pharm Res. 2012;29:3090-101 pubmed publisher
    To evaluate the antitumor efficacy of solid lipid nanoparticle-encapsulated phospho-sulindac (SLN-PS) in human lung cancer. PS was incorporated into SLNs using the emulsion evaporation technique...
  45. Athar M, An K, Tang X, Morel K, Kim A, Kopelovich L, et al. Photoprotective effects of sulindac against ultraviolet B-induced phototoxicity in the skin of SKH-1 hairless mice. Toxicol Appl Pharmacol. 2004;195:370-8 pubmed
    b>Sulindac is a nonsteroidal anti-inflammatory drug with demonstrated potency as a chemopreventive agent in animal models of carcinogenesis and in patients with familial adenomatous polyposis...
  46. Yang W, Bancroft L, Augenlicht L. Methylation in the p21WAF1/cip1 promoter of Apc+/-, p21+/- mice and lack of response to sulindac. Oncogene. 2005;24:2104-9 pubmed
    ..and that inactivation of only one p21 allele was also sufficient to abrogate duodenal tumor inhibition by sulindac, a nonsteroidal anti-inflammatory drug...
  47. Kim D, Prabhu K, Gonzalez F, Peters J. Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). Carcinogenesis. 2006;27:1105-12 pubmed
    ..32 g sulindac/kg diet...
  48. Matsumoto T, Nakamura S, Esaki M, Yao T, Iida M. Effect of the non-steroidal anti-inflammatory drug sulindac on colorectal adenomas of uncolectomized familial adenomatous polyposis. J Gastroenterol Hepatol. 2006;21:251-7 pubmed
    The aim of the present study was to elucidate the effect of sulindac on uncolectomized familial adenomatous polyposis (FAP). Seven FAP patients (SU group) without proctocolectomy were given sulindac 300 mg/day orally for 12 months...
  49. Felts A, Ji C, Stafford J, Crews B, Kingsley P, Rouzer C, et al. Desmethyl derivatives of indomethacin and sulindac as probes for cyclooxygenase-dependent biology. ACS Chem Biol. 2007;2:479-83 pubmed
    ..Potent COX inhibitors exist, but they display off-target effects. 2'-Desmethyl derivatives of indomethacin and sulindac sulfide were synthesized that demonstrated reduced COX inhibitory activity but were inducers of peroxisome ..
  50. Yang W, Velcich A, Mariadason J, Nicholas C, Corner G, Houston M, et al. p21(WAF1/cip1) is an important determinant of intestinal cell response to sulindac in vitro and in vivo. Cancer Res. 2001;61:6297-302 pubmed
    b>Sulindac, a nonsteroidal anti-inflammatory drug, inhibits intestinal tumorigenesis in humans and rodents. Sulindac induced complex alterations in gene expression, but only 0...
  51. Gurpinar E, Grizzle W, Shacka J, Mader B, Li N, Piazza N, et al. A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy. Mol Cancer Ther. 2013;12:663-74 pubmed publisher
    Nonsteroidal anti-inflammatory drugs such as sulindac sulfide have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from COX inhibition limit their use in cancer therapy...
  52. Walker D, Siddique I, Anderson H, Gardiner T, Archer D, Boulton AJM -, et al. Nerve pathology in the type 1 diabetic dog: effects of treatment with sulindac. J Peripher Nerv Syst. 2001;6:219-26 pubmed
    ..of a large animal model of long-duration type 1 diabetes and also to determine the effects of treatment with sulindac. Detailed morphometric studies were performed to define nerve fiber and endoneurial capillary pathology in 6 ..
  53. Berman K, Verma U, Harburg G, Minna J, Cobb M, Gaynor R. Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-kappaB. Clin Cancer Res. 2002;8:354-60 pubmed
    ..Recently, sulindac and other nonsteroidal anti-inflammatory drugs have been shown to inhibit tumor necrosis factor (TNF)-alpha-..
  54. Sinicrope F, Penington R. Sulindac sulfide-induced apoptosis is enhanced by a small-molecule Bcl-2 inhibitor and by TRAIL in human colon cancer cells overexpressing Bcl-2. Mol Cancer Ther. 2005;4:1475-83 pubmed
    b>Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that induces apoptosis in cultured colon cancer cells and in intestinal epithelia in association with its chemopreventive efficacy...
  55. Yasui H, Adachi M, Imai K. Combination of tumor necrosis factor-alpha with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice. Cancer. 2003;97:1412-20 pubmed
    ..Recently, a nonsteroidal antiinflammatory drug, sulindac, and its metabolites have been shown to inhibit the NF-kappaB pathway and to enhance TNF-alpha-mediated apoptosis ..
  56. Flis S, Spłwiński J. Inhibitory effects of 5-fluorouracil and oxaliplatin on human colorectal cancer cell survival are synergistically enhanced by sulindac sulfide. Anticancer Res. 2009;29:435-41 pubmed
    ..was to compare growth inhibitory effects of cytostatics (5-fluorouracil, 5-FU; oxaliplatin) and COX inhibitor sulindac sulfide (an active metabolite of sulindac), given alone or in combination, on several CRC cell lines...
  57. Kim J, Baek S, Sali T, Eling T. The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15. Mol Cancer Ther. 2005;4:487-93 pubmed
    ..b>Sulindac sulfide was the most significant NSAID activated gene 1 (NAG-1) inducer and its expression was inversely ..
  58. Ignatenko N, Besselsen D, Stringer D, Blohm Mangone K, Cui H, Gerner E. Combination chemoprevention of intestinal carcinogenesis in a murine model of familial adenomatous polyposis. Nutr Cancer. 2008;60 Suppl 1:30-5 pubmed publisher
    ..Treatment with the nonsteroidal anti-inflammatory drugs (NSAIDS) sulindac or celecoxib can suppress polyp development in FAP patients, but responses are generally transient and incomplete...
  59. Thompson P, Wertheim B, Zell J, Chen W, McLaren C, Lafleur B, et al. Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology. 2010;139:797-805, 805.e1 pubmed publisher
    ..We studied effects of the combination of difluoromethylornithine (DFMO) and sulindac on biomarkers and investigated factors that modify their efficacy...
  60. Jarvis M, Gray T, Palmer C. Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line. Oncogene. 2005;24:8211-5 pubmed
    Nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac sulfide are known to exert cancer chemopreventative activity in a range of cell lines...
  61. Jacoby R, Cole C, Hawk E, Lubet R. Ursodeoxycholate/Sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis. Gastroenterology. 2004;127:838-44 pubmed
    ..epidemiological data, and clinical trials in patients with adenomatous polyposis have consistently indicated that sulindac and other nonsteroidal antiinflammatory drugs or cyclooxygenase inhibitors have the greatest potential efficacy ..
  62. Nikitakis N, Hebert C, Lopes M, Reynolds M, Sauk J. PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells. Int J Cancer. 2002;98:817-23 pubmed
    There is strong evidence that nonsteroidal antiinflammatory drug (NSAID) sulindac may exert a significant antineoplastic effect...
  63. Kunte D, Wali R, Koetsier J, Roy H. Antiproliferative effect of sulindac in colonic neoplasia prevention: role of COOH-terminal Src kinase. Mol Cancer Ther. 2008;7:1797-806 pubmed publisher
    ..In the azoxymethane-treated rat model of experimental colon carcinogenesis, sulindac treatment markedly induced Csk with a corresponding increase in inhibitory phosphorylation of Src (Tyr(527))...
  64. Rice P, Beard K, Driggers L, Ahnen D. Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites. Cancer Res. 2004;64:8148-51 pubmed
    Nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac have shown potent chemopreventive and tumor regressive effects against colorectal cancer, the second leading cause of cancer death in the United States...
  65. Cheng K, Mattheolabakis G, Wong C, Ouyang N, Huang L, Constantinides P, et al. Topical phospho-sulindac (OXT-328) is effective in the treatment of non-melanoma skin cancer. Int J Oncol. 2012;41:1199-203 pubmed publisher
    Phospho-sulindac (P-S, OXT-328), a novel sulindac derivative, has shown superior anticancer efficacy and safety compared to sulindac...
  66. Zou W, Beggs K, Sparkenbaugh E, Jones A, Younis H, Roth R, et al. Sulindac metabolism and synergy with tumor necrosis factor-alpha in a drug-inflammation interaction model of idiosyncratic liver injury. J Pharmacol Exp Ther. 2009;331:114-21 pubmed publisher
    b>Sulindac (SLD) is a nonsteroidal anti-inflammatory drug (NSAID) that has been associated with a greater incidence of idiosyncratic hepatotoxicity in human patients than other NSAIDs...
  67. Yip Schneider M, Schmidt C. MEK inhibition of pancreatic carcinoma cells by U0126 and its effect in combination with sulindac. Pancreas. 2003;27:337-44 pubmed
    ..We therefore evaluated the effect of treating pancreatic tumor cells with the combination of the NSAID sulindac and U0126. Treatment with U0126 complemented sulindac-induced growth inhibition in BxPC-3 and PANC-1 cells...
  68. Karl T, Seibert N, Stohr M, Osswald H, Rösl F, Finzer P. Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007;245:103-11 pubmed
    b>Sulindac, a nonsteroidal anti-inflammatory drug (NSAID), induces growth arrest in HeLa cells and causes strong inhibition of the G1 to S transition of the cell cycle in a concentration-dependent manner...
  69. Humphrey R, Bartfield M, Carlan S, O Brien W, O Leary T, Triana T. Sulindac to prevent recurrent preterm labor: a randomized controlled trial. Obstet Gynecol. 2001;98:555-62 pubmed
    To assess the efficacy of oral sulindac in low doses for prolonged duration to decrease the risk of recurrent preterm labor and extend gestation...
  70. Zell J, Pelot D, Chen W, McLaren C, Gerner E, Meyskens F. Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila). 2009;2:209-12 pubmed publisher
    ..of baseline CV risk on adverse CV events in a phase III trial of difluoromethylornithine (DFMO) plus the NSAID sulindac versus placebo in preventing colorectal adenomas. Trial data were analyzed to determine baseline CV risk...
  71. Jung B, Barbier V, Brickner H, Welsh J, Fotedar A, McClelland M. Mechanisms of sulindac-induced apoptosis and cell cycle arrest. Cancer Lett. 2005;219:15-25 pubmed
    The mechanism underlying the chemopreventive effects of the non-steroidal anti-inflammatory drug sulindac remains unclear. Its active metabolite, sulindac sulfide, induces cell cycle arrest as well as apoptosis in mammalian cell lines...
  72. Minami T, Adachi M, Kawamura R, Zhang Y, Shinomura Y, Imai K. Sulindac enhances the proteasome inhibitor bortezomib-mediated oxidative stress and anticancer activity. Clin Cancer Res. 2005;11:5248-56 pubmed
    The nonsteroidal antiinflammatory drug sulindac is a promising chemopreventive agent against colon cancer...
  73. Yasui H, Adachi M, Imai K. Combination of tumor necrosis factor-alpha with sulindac in human carcinoma cells in vivo. Ann N Y Acad Sci. 2003;1010:273-7 pubmed
    ..Recently, the nonsteroidal anti-inflammatory drug (NSAID) sulindac and its metabolites have been shown to inhibit the NF-kappaB-mediated survival signals through inhibition of IKK-..
  74. Dairam A, Müller A, Daya S. Non-steroidal anti-inflammatory agents, tolmetin and sulindac attenuate quinolinic acid (QA)-induced oxidative stress in primary hippocampal neurons and reduce QA-induced spatial reference memory deficits in male Wistar rats. Life Sci. 2007;80:1431-8 pubmed
    ..In the present study, the possible neuroprotective properties of tolmetin and sulindac were investigated using quinolinic acid (QA)-induced neurotoxicity as well as behavioral studies...
  75. Vogt T, McClelland M, Jung B, Popova S, Bogenrieder T, Becker B, et al. Progression and NSAID-induced apoptosis in malignant melanomas are independent of cyclooxygenase II. Melanoma Res. 2001;11:587-99 pubmed
    ..However, in vitro the Cox-inhibiting non-steroidal anti-inflammatory drug (NSAID) sulindac sulphide (SIS) was significantly more effective in inducing apoptosis than sulindac sulphone (SOS), a derivative ..
  76. Bock J, Menon S, Goswami P, Sinclair L, Bedford N, Jackson R, et al. Differential activity of sulindac metabolites against squamous cell carcinoma of the head and neck is mediated by p21waf1/cip1 induction and cell cycle inhibition. Cancer Biol Ther. 2007;6:30-9 pubmed
    b>Sulindac sulfide and sulindac sulfone have demonstrated anti-neoplastic and chemo-preventive activity against various human tumors, but few studies have examined the relative effectiveness of these drugs against squamous cell carcinoma of ..
  77. Jakubowska Mućka A, Sienko J, Switaj T, Gołąb J, Lasek W. [Antitumor effects of sulindac in ovarian cell cultures]. Ginekol Pol. 2011;82:195-9 pubmed
    ..Cytotoxic effect of NSAIDs was tested using MTT colorimetric assay. Amongst 6 NSAIDs tested: sulindac, sulindac sulfide, sulindac sulfone, acetylsalicylic acid, nimesulide, and rofecoxib, viability of ovarian ..
  78. Ohishi T, Kishimoto Y, Miura N, Shiota G, Kohri T, Hara Y, et al. Synergistic effects of (-)-epigallocatechin gallate with sulindac against colon carcinogenesis of rats treated with azoxymethane. Cancer Lett. 2002;177:49-56 pubmed
    ..b>Sulindac is also well known as a cancer-preventive agent against colon cancer, but its usage is restricted because of its ..
  79. Han A, Song Z, Tong C, Hu D, Bi X, Augenlicht L, et al. Sulindac suppresses beta-catenin expression in human cancer cells. Eur J Pharmacol. 2008;583:26-31 pubmed publisher
    b>Sulindac has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells...
  80. Esaki M, Matsumoto T, Mizuno M, Kobori Y, Yoshimura R, Yao T, et al. Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a case. Dis Colon Rectum. 2002;45:1397-402; discussion 1402-6 pubmed
    ..We report a patient with attenuated familial adenomatous polyposis who has been treated with sulindac for five years...
  81. Bottone F, Martinez J, Collins J, Afshari C, Eling T. Gene modulation by the cyclooxygenase inhibitor, sulindac sulfide, in human colorectal carcinoma cells: possible link to apoptosis. J Biol Chem. 2003;278:25790-801 pubmed
    ..One novel hypothesis is alterations in gene expression. To test this hypothesis sulindac sulfide, which is used to treat familial adenomatous polyposis, was selected to detect gene modulation in human ..
  82. Hughes A, Smith N, Wallace H. Polyamines reverse non-steroidal anti-inflammatory drug-induced toxicity in human colorectal cancer cells. Biochem J. 2003;374:481-8 pubmed
    Naproxen, sulindac and salicylate, three NSAIDs (non-steroidal anti-inflammatory drugs), were cytotoxic to human colorectal cancer cells in culture. Toxicity was accompanied by significant depletion of intracellular polyamine content...
  83. Boon E, Keller J, Wormhoudt T, Giardiello F, Offerhaus G, van der Neut R, et al. Sulindac targets nuclear beta-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines. Br J Cancer. 2004;90:224-9 pubmed
    ..Therefore, the effect of the NSAID sulindac on nuclear (nonphosphorylated) beta-catenin and beta-catenin/TCF-mediated transcription was investigated...
  84. Piazza G, Keeton A, Tinsley H, Gary B, Whitt J, Mathew B, et al. A novel sulindac derivative that does not inhibit cyclooxygenases but potently inhibits colon tumor cell growth and induces apoptosis with antitumor activity. Cancer Prev Res (Phila). 2009;2:572-80 pubmed publisher
    Nonsteroidal anti-inflammatory drugs such as sulindac have shown promising antineoplastic activity, although toxicity from cyclooxygenase (COX) inhibition and the suppression of prostaglandin synthesis limits their use for chemoprevention...
  85. Shigeoka Y, Igishi T, Matsumoto S, Nakanishi H, Kodani M, Yasuda K, et al. Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-beta through Akt inhibition. J Cancer Res Clin Oncol. 2004;130:146-52 pubmed
    ..Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to interfere with ..
  86. Zhang T, Fields J, Ehrlich S, Boman B. The chemopreventive agent sulindac attenuates expression of the antiapoptotic protein survivin in colorectal carcinoma cells. J Pharmacol Exp Ther. 2004;308:434-7 pubmed
    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac have chemopreventive activity against colorectal tumors...