Inhibition of Epstein–Barr virus early antigen activation promoted by 12-O-tetradecanoylphorbol-13-acetate by the non-steroidal anti-inflammatory drugs
| Autor: | Takao Konoshima, J. Takayasu, Govind J. Kapadia, Magnus A. Azuine, Midori Takasaki, Harukuni Tokuda, Hoyoku Nishino |
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| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
Cell Survival Acetates Pharmacology medicine.disease_cause 12-O-Tetradecanoylphorbol-13-acetate Structure-Activity Relationship chemistry.chemical_compound Sulindac Neoplasms Tumor Cells Cultured medicine Humans Etodolac Fluorescent Antibody Technique Indirect Antigens Viral Anticarcinogen Carcinogen Chemistry Anti-Inflammatory Agents Non-Steroidal Carcinoma Cancer Benzene Nasopharyngeal Neoplasms medicine.disease Salicylates Oncology Biochemistry Tetradecanoylphorbol Acetate Carcinogens Carcinogenesis Oxidation-Reduction medicine.drug |
| Zdroj: | Cancer Letters. 161:221-229 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/s0304-3835(00)00616-9 |
| Popis: | As part of our screening program for cancer inhibitory agents effective specifically in the promotion stage of cancer development, we have evaluated the possible inhibitory effects of 36 non-steroidal anti-inflammatory drugs (NSAIDs) on the Epstein-Barr virus early antigen (EBV-EA) activation which was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. All the drugs were observed to inhibit the EBV-EA activation at low doses with low toxicity. The two most active anti-tumor promoting agents were the arylacetic acid derivatives, etodolac and sulindac. We also report for the first time the activities of 14 new NSAIDs belonging to different classes as potential cancer chemopreventive agents. A structure-activity relationship study showed that among the salicylic acid derivative tested, the oxidation of the thiol group to dithiol derivatives results in the reduction of the activity. Introduction of amino group on the salicylic acid molecules also results in the reduction of activity in the EBV-EA assay. The results are of great interest in the development of NSAIDs as cancer chemopreventive agents, which halt cancer progression in multistage carcinogenesis, where successive activities are required to evolve into fully-fledged and metastatic cancer. |
| Databáze: | OpenAIRE |
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