(±)-Gossypol induces apoptosis and autophagy in head and neck carcinoma cell lines and inhibits the growth of transplanted salivary gland cancer cells in BALB/c mice

Abstract

Racemic Gossypol [(±)-GOS], composed of both (−)-GOS and (+)-GOS, is a small BH3-mimetic polyphenol derived from cotton seeds. (±)-GOS has been employed and well tolerated by cancer patients. Head and neck carcinoma (HNC) represents one of the most fatal cancers worldwide, and a significant proportion of HNC expresses high levels of antiapoptotic Bcl-2 proteins. In this study, we demonstrate that (±)-GOS inhibits cell proliferation and induces apoptosis and autophagy of human pharynx, tongue, and salivary gland cancer cell lines and of mouse salivary gland cancer cells (SALTO). (±)-GOS was able to: (a) decrease the ErbB2 protein expression; (b) inhibit the phosphorylation of ERK1/2 and AKT; (c) stimulate p38 and JNK1/2 protein phosphorylation. (±)-GOS administration was safe in BALB/c mice and it reduced the growth of transplanted SALTO cells in vivo and prolonged mice median survival. Our results suggest the potential role of (±)-GOS as an antitumor agent in HNC patients.

Keywords:

• Head and neck cancer
• (±)-Gossypol
• BH3-mimetic compound
• autophagy
• BALB/c mice

Acknowledgements

We thank Mrs K. Bibbey for help in English language editing. SALTO cells were kindly provided by Prof. Federica Cavallo (University of Torino), Prof. Pier Luigi Lollini, and Prof. Patrizia Nanni (University of Bologna). Rosanna Mattera is recipient of the Sapienza PhD program in Molecular Medicine.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.