Inhibition of Epstein–Barr virus early antigen activation promoted by 12- O-tetradecanoylphorbol-13-acetate by the non-steroidal anti-inflammatory drugs

• Published in: Cancer letters Vol. 161; no. 2; pp. 221 - 229
• Main Authors: Kapadia, Govind J, Azuine, Magnus A, Takayasu, Jyunko, Konoshima, Takao, Takasaki, Midori, Nishino, Hoyoku, Tokuda, Harukuni
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20-12-2000; Elsevier
• Subjects: Acetates - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antigens, Viral - metabolism; Benzene - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cancer; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Carcinoma - metabolism; Cell Survival - drug effects; Chemoprevention; early antigen; Epstein-Barr virus; Epstein–Barr virus activation; etodolac; Etodolac - pharmacology; Fluorescent Antibody Technique, Indirect; Foods and miscellaneous; Humans; Inhibition; Medical sciences; Nasopharyngeal Neoplasms - metabolism; Neoplasms - prevention & control; Non-steroidal anti-inflammatory drugs; Oxidation-Reduction; Pharmacology. Drug treatments; Salicylates - pharmacology; Structure-activity; Structure-Activity Relationship; sulindac; Sulindac - pharmacology; Tetradecanoylphorbol Acetate; TPA; Tumor Cells, Cultured; Tumors; Epstein–Barr virus activation; Structure-activity; Inhibition; Chemoprevention; Non-steroidal anti-inflammatory drugs; Cancer; Gammaherpesvirinae; Toxicity; Herpesviridae; Early antigen; Activation; Epstein Barr virus; Malignant tumor; Anticarcinogen; Carcinogenesis; Virus; Non steroidal antiinflammatory agent; Prevention; Carcinogen; Structure activity relation
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(00)00616-9

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.