(-)-Gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo

Keith G. Wolter, Steven J. Wang, Bradley S. Henson, Shaomeng Wang, Kent A. Griffith, Bhavna Kumar, Jianyong Chen, Thomas E. Carey, Carol R. Bradford, Nisha J. D'Silva

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC). Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as Bcl-xL. (-)-Gossypol, the negative enantiomer of a cottonseed polyphenol, binds to Bcl-xL and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (-)-gossypol in an orthotopic xenograft model of HNSCC, using two human HNSCC cell lines with high Bcl-xL expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (-)-gossypol treatment groups (5 and 15 mg/kg). Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (-)-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (-)-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (-)-gossypol treatment. Our results demonstrate that (-)-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalNeoplasia
Volume8
Issue number3
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • (-)-Gossypol
  • Bcl-x
  • Chemoresistance
  • Head and neck cancer
  • Oral cancer

ASJC Scopus subject areas

  • Cancer Research

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