Bcl-xL inhibits p53- but not apoptin-induced apoptosis in head and neck squamous cell carcinoma cell line.
Nonfunctional p53 and especially upregulation of Bcl-x(L) result in advanced disease and poor prognosis of patients suffering head and neck squamous cell carcinoma (HNSCC). Aberrancies of Bcl-x(L) and/or p53 in HNSCC lead to inability of anticancer drugs to induce apoptosis. Bcl-x(L) and/or mutated p53 inhibit the apoptotic process by preventing the mitochondrial release of cytochrome c and/or activation of execution caspases. Here, we report that expression of the avian virus-derived apoptin protein resulted in induction of apoptosis in the HNSCC-derived cell line UMSSC-14B despite the presence of nonfunctional p53. Apoptin activated the execution caspase 3 and induced the release of mitochondrial cytochrome c. Upregulation of Bcl-x(L) in UMSCC-14B cells did not interfere with the apoptin-induced apoptosis, whereas it clearly negatively affected the p53-induced one. Bcl-x(L) significantly decreased the p53-induced cytochrome c release, but not the apoptin-triggered one. Our data demonstrate that apoptin induces apoptosis independent of Bcl-x(L) and p53 and may constitute a potential therapeutic agent for treatment of HNSCC.
Schoop
Remilio A L
RA
Department of Otolaryngology and Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Kooistra
Klaas
K
Baatenburg De Jong
Robert J
RJ
Noteborn
Mathieu H M
MH
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D036022:Capsid Proteins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D036022:Capsid Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C091717:VP3 protein, Chicken anemia virus; D051020:bcl-X Protein; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases