BMS-275183-induced gene expression patterns in head and neck carcinoma.
OBJECTIVE
BMS-275183 is an orally bioavailable taxane that has antitumor activity in preclinical cancer models. However, limited BMS-275183 studies have been performed in head and neck squamous cell carcinoma (HNSCC) cell lines. The purpose of this study is to identify the biological activity of BMS-275183 on HNSCC.


METHODS
Head and neck squamous cell carcinoma cell lines, HN6, HN12, and HN30, were exposed to BMS-275183. BMS-275183-induced growth suppression, cell-cycle arrest, and apoptosis were measured. Then, expression of selected proteins that were induced by BMS-275183 was determined by Western blot analysis.


RESULTS
BMS-275183 suppressed proliferation and induced G(2)M arrest and apoptosis in all HNSCC cell lines tested. BMS-275183 altered the expression of cell-cycle regulators, such as cyclin A and cyclin B1. The expression of E2F and p27 was decreased and increased, respectively, in all HNSCC cell lines. Cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) were increased in HN6 and HN12 cells. epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) expression were decreased by BMS-275183 in HN6 and HN30 cell lines, whereas phosphorylated epidermal growth factor receptor (pEGFR) was decreased in only HN6 cells.


CONCLUSIONS
BMS-275183 induced cellular apoptosis, cell-cycle arrest, and altered gene expression in HNSCC via molecular pathways similar to other taxanes. These preclinical experiments suggest that BMS-275183 may be useful in treating HNSCC and that the aforementioned genes can potentially be used as surrogate end-point biomarkers.
Yoo
George H
GH
Department of Otolaryngology--Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI 48201, USA. gyoo@med.wayne.edu
Tran
Vivian R
VR
Lemonnier
Lori A
LA
Ezzat
Waleed H
WH
Subramanian
Geetha
G
Piechocki
Marie P
MP
Ensley
John F
JF
Lonardo
Fulvio
F
Kim
Harold
H
Lin
Ho-Sheng
HS
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured