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 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.
Chun
Kyung-Hee
KH
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Lee
Ho-Young
HY
Hassan
Khaled
K
Khuri
Fadlo
F
Hong
Waun Ki
WK
Lotan
Reuben
R
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein; D003986:Dibenzocycloheptenes
D019883:Alkyl and Aryl Transferases; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D010880:Piperidines; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051020:bcl-X Protein; C494811:BCL2L1 protein, human; C494918:AKT1 protein, human; C115354:lonafarnib; D003986:Dibenzocycloheptenes