Abstract
The farnesyltransferase inhibitor SCH66336 exhibits antitumor activity in vitro and in vivo; however, its mechanism of action is still unresolved. We found that SCH66336 suppressed growth and induced apoptosis of human head and neck squamous carcinoma cells (HNSCC). SCH66336 suppressed protein kinase B/Akt activity as well as the phosphorylation of the Akt substrates glycogen synthase kinase (GSK)-3 beta, forkhead transcription factor, and BAD. Infection of SqCC/Y1 cells with an adenovirus that contained a constitutively active form of Akt rescued cells from SCH66336-induced apoptosis. These results suggest that SCH66336 is a potent apoptosis inducer in HNSCC cells and that it may act by suppressing the Akt pathway.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Apoptosis / drug effects*
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Carcinoma, Squamous Cell / drug therapy
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Carcinoma, Squamous Cell / pathology*
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Enzyme Inhibitors / pharmacology*
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Farnesyltranstransferase
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Head and Neck Neoplasms / drug therapy
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Head and Neck Neoplasms / pathology*
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Humans
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Piperidines / pharmacology*
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
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Pyridines / pharmacology*
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Tumor Cells, Cultured
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Enzyme Inhibitors
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Piperidines
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Pyridines
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bcl-X Protein
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Alkyl and Aryl Transferases
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Farnesyltranstransferase
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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lonafarnib