BMS-275183-induced gene expression patterns in head and neck carcinoma.

Abstract

PURPOSE:

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.

MATERIALS AND 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.

• Authors: George H Yoo, Vivian R Tran, Lori A Lemonnier, Waleed H Ezzat, Geetha Subramanian, Marie P Piechocki, John F Ensley, Fulvio Lonardo, Harold Kim, Ho-Sheng Lin
• Journal: American journal of otolaryngology (Am J Otolaryngol) 2007 Sep-Oct Vol. 28 Issue 5 Pg. 309-15 ISSN: 0196-0709 [Print] United States
• PMID: 17826531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Annexin A5
• BMS-275183
• Bridged-Ring Compounds
• Intercellular Signaling Peptides and Proteins
• Neoplasm Proteins
• Taxoids

Topics

• Annexin A5 (metabolism)
• Apoptosis (drug effects)
• Blotting, Western
• Bridged-Ring Compounds (pharmacology)
• Cell Cycle (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Head and Neck Neoplasms (genetics, metabolism)
• Humans
• Intercellular Signaling Peptides and Proteins (metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Taxoids (pharmacology)
• Tumor Cells, Cultured