Chemotherapeutic Properties of Phospho-Nonsteroidal Anti-Inflammatory Drugs, a New Class of Anticancer Compounds
| Autor: | Yu Sun, Nengtai Ouyang, Despina Komninou, Gerardo G. Mackenzie, Gang Xie, Basil Rigas, Kvetoslava Vrankova, Liqun Huang |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Thioredoxin-Disulfide Reductase Time Factors medicine.drug_class Immunoblotting Mice Nude Apoptosis Pharmacology Biology medicine.disease_cause Article Anti-inflammatory Mice Sulindac Thioredoxins In vivo Cell Line Tumor Neoplasms Pancreatic cancer medicine Animals Humans skin and connective tissue diseases Cell Proliferation Mice Inbred BALB C Aspirin Dose-Response Relationship Drug Molecular Structure Cell growth Anti-Inflammatory Agents Non-Steroidal NF-kappa B medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays Organophosphates digestive system diseases Oncology Female Thioredoxin HT29 Cells Oxidative stress medicine.drug |
| Zdroj: | Cancer Research. 71:7617-7627 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Nonsteroidal anti-inflammatory drugs (NSAID) exhibit antineoplastic properties, but conventional NSAIDs do not fully meet safety and efficacy criteria for use as anticancer agents. In this study, we evaluated the chemotherapeutic efficacy of 5 novel phospho-NSAIDs, each of which includes in addition to the NSAID moiety a diethylphosphate linked through a butane moiety. All 5 compounds inhibited the growth of human breast, colon, and pancreatic cancer cell lines with micromolar potency. In vivo investigations confirmed the antitumor activity of phospho-aspirin (PA) and phospho-sulindac (PS) in inhibiting tumor growth in established human xenograft models, in which cell proliferation was suppressed and apoptosis enhanced in the absence of detectable animal toxicity. Notably, all of the phospho-NSAIDs tested induced reactive oxygen and nitrogen species in cultured cells, with PA and PS inducing detectable levels of oxidative stress in vivo that were associated positively with apoptosis and negatively with proliferation. Potentially explaining these effects, all of the phospho-NSAIDs tested also inhibited the thioredoxin system and the redox sensitive transcription factor NF-κB. Taken together, our findings show the strong anticancer efficacy and promising safety of phospho-NSAIDs in preclinical models of breast, colon, and pancreatic cancer, suggesting further evaluation as anticancer agents. Cancer Res; 71(24); 7617–27. ©2011 AACR. |
| Databáze: | OpenAIRE |
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