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

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-x(L). (-)-gossypol, the negative enantiomer of a cottonseed polyphenol, binds to Bcl-x(L) 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-x(L) 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.

• Publication year

  2006

• Venue

  Neoplasia

• Publication date

  2006-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1593/NEO.05691PMID 16611409PMCID PMC1578526
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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