Increased level of the p67phox subunit of NADPH oxidase by 4HPR in head and neck squamous carcinoma cells.
N-(4-hydroxyphenyl)retinamide (4HPR) is a synthetic retinoid that has shown efficacy in cancer chemoprevention and therapy possibly due to its ability to induce growth inhibition and apoptosis in cancer cells. Reactive oxygen species (ROS) have been implicated in mediating 4HPR-induced apoptosis in various cancer cells, including head and neck squamous cell carcinoma (HNSCC) cells. 4HPR increased the level of p67phox, which is a subunit of the NADPH oxidase complex that is involved in the generation of ROS. The increase in the level of p67phox protein may be a downstream effect of the activation of c-Jun N-terminal kinase (JNK) induced by 4HPR. Suppression of endogenous and 4HPR-induced levels of p67phox using small interfering RNA did not result in a change in ROS generation or apoptosis. These results suggest that p67phox is not a critical component or a limiting factor in the 4HPR-induced apoptosis pathway in HNSCC cells.
Kim
Hyun-Jung
HJ
Department of Thoracic/Head and Neck Medical Oncology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Oridate
Nobuhiko
N
Lotan
Reuben
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D017313:Fenretinide / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000970:Antineoplastic Agents; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; D017313:Fenretinide; D019255:NADPH Oxidases; D048031:JNK Mitogen-Activated Protein Kinases