Implication of protein kinase B/Akt and Bcl-2/Bcl-XL suppression by the farnesyl transferase inhibitor SCH66336 in apoptosis induction in squamous carcinoma cells

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 kinas...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2003-08, Vol.63 (16), p.4796-4800
Main Authors: CHUN, Kyung-Hee, LEE, Ho-Young, HASSAN, Khaled, KHURI, Fadlo, WAUN KI HONG, LOTAN, Reuben
Format: Article
Language:English
Subjects:
Alkyl and Aryl Transferases - antagonists & inhibitors
Antineoplastic agents
Apoptosis - drug effects
bcl-X Protein
Biological and medical sciences
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - pathology
Chemotherapy
Enzyme Inhibitors - pharmacology
Farnesyltranstransferase
head and neck carcinoma
Head and Neck Neoplasms - drug therapy
Head and Neck Neoplasms - pathology
Humans
Medical sciences
Pharmacology. Drug treatments
Piperidines - pharmacology
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - antagonists & inhibitors
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
Pyridines - pharmacology
Tumor Cells, Cultured
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Summary: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.
ISSN:0008-5472
1538-7445