N-acetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer

Oral Oncol. 2013 Feb;49(2):129-35. doi: 10.1016/j.oraloncology.2012.08.003. Epub 2012 Sep 1.

Abstract

Objectives: Overexpression of the epidermal growth factor (EGF) receptor (EGFR) gene in the squamous cell carcinomas of the head and neck (SCCHN) is often associated with inauspicious prognosis and poor survival. N-acetylcysteine (NAC), a compound from some vegetables and allium species, appears anti-tumorigenesis, but the underlying mechanism is unclear. The objective of this study is to investigate the role of NAC in EGFR-overexpressing oral cancer.

Materials and methods: Both HSC-3 and SCC-4 human tongue squamous carcinoma cell lines and an HSC-3 xenograft mouse model were used to test the anti-growth efficacy of NAC in vitro and in vivo, respectively.

Results: NAC treatment suppressed cell growth, with concomitantly increased expression of HMG box-containing protein 1 (HBP1), a transcription suppressor, and decreased EGFR/Akt activation, in EGFR-overexpressing HSC-3 oral cancer cells. HBP1 knockdown attenuated the growth arrest and apoptosis induced by NAC. Lastly, NAC and AG1478, an EGFR inhibitor, additively suppressed colony formation in HSC-3 cells.

Conclusion: Taken together, our data indicate that NAC exerts its growth-inhibitory function through modulating EGFR/Akt signaling and HBP1 expression in EGFR-overexpressing oral cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Apoptosis
  • Base Sequence
  • Cell Cycle
  • Cell Division / drug effects*
  • DNA Primers
  • ErbB Receptors / metabolism*
  • Gene Knockdown Techniques
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*

Substances

  • DNA Primers
  • HBP1 protein, human
  • High Mobility Group Proteins
  • Repressor Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • Acetylcysteine