Apoptin induces apoptosis in an oral cancer mouse model.
Apoptin, a chicken anemia virus-derived protein, induces apoptosis in various tumor cell lines and xenografted tumors. Its apoptotic activity is not hampered by tumor-suppressor p53 mutations or overexpression of anti-apoptosis proteins Bcl-2 or Bcl-x(L). We report for the first time the effects of apoptin expression in primary oral tumors, induced by the carcinogen 4-Nitroquinoline- 1-oxide in immunocompetent mice. In vivo a significant amount of primary oral tumor cells expressing apoptin cells underwent apoptosis, whereas synthesis of the LacZ control product did not. Ectopical expression of apoptin in passage 1 cell cultures derived from these oral tumors also resulted in apoptin-induced. Both in-vivo and in-vitro treated cells underwent apoptosis via the activation of caspase-3. The fact that apoptin induces apoptosis in primary squamous cell carcinoma cells indicates that apoptin is a potential therapeutic agent for treatment of head and neck squamous cell carcinoma.
Schoop
Remilio A L
RA
Department of Otolaryngology, Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands. r.a.l.schoop@lumc.nl
Baatenburg de Jong
Robert J
RJ
Noteborn
Mathieu H M
MH
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D036022:Capsid Proteins / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D010865:Pilot Projects; D010957:Plasmids; D011897:Random Allocation; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
D036022:Capsid Proteins; D002273:Carcinogens; D005456:Fluorescent Dyes; C091717:VP3 protein, Chicken anemia virus; D015112:4-Nitroquinoline-1-oxide; D053148:Caspase 3; D016650:Fluorescein-5-isothiocyanate