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

Neoplasia. 2006 Mar;8(3):163-72. doi: 10.1593/neo.05691.


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 types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / transplantation
  • Cells, Cultured / drug effects
  • Gossypol / administration & dosage
  • Gossypol / pharmacology
  • Gossypol / therapeutic use*
  • Humans
  • Injections, Intraperitoneal
  • Keratinocytes / drug effects
  • Laryngeal Neoplasms / drug therapy*
  • Laryngeal Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Mitotic Index
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Neoplasm Proteins / antagonists & inhibitors*
  • Random Allocation
  • Xenograft Model Antitumor Assays
  • bcl-X Protein / antagonists & inhibitors*


  • Antineoplastic Agents, Phytogenic
  • BCL2L1 protein, human
  • Neoplasm Proteins
  • bcl-X Protein
  • Gossypol