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

Yoo, George H.; Tran, Vivian R.; Lemonnier, Lori A.; Ezzat, Waleed H.; Subramanian, Geetha; Piechocki, Marie P.; Ensley, John F.; Lonardo, Fulvio; Kim, Harold; Lin, Ho-Sheng

doi:10.1016/j.amjoto.2006.10.001

« Previous Next »American Journal of Otolaryngology - Head and Neck Medicine and Surgery
Volume 28, Issue 5 , Pages 309-315, September 2007

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

George H. Yoo, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
- Corresponding author. Department of Otolaryngology-Head and Neck Surgery, Wayne State University, 4201 St. Antoine, 5 E University Health Center, Detroit, MI 48201, USA. Tel.: +1 313 745 4336; fax: +1 313 577 8555.
Vivian R. Tran, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Lori A. Lemonnier, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Waleed H. Ezzat, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Geetha Subramanian, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Marie P. Piechocki, PhD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
John F. Ensley, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
- Division of Hematology/Oncology, Department of Medicine, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
Fulvio Lonardo, MD
- Department of Pathology, Wayne State University, Detroit, MI, USA
Harold Kim, MD
- Department of Radiation Oncology, Wayne State University, Detroit, MI, USA
Ho-Sheng Lin, MD
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University and Karmanos Cancer Institute, Detroit, MI, USA
- Department of Surgery, John D. Dingell VA Medical Center, Detroit, MI, USA

Received 27 July 2006

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 G₂M 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.