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

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.

• Authors: Ming-Fen Lee, Chien-Yi Chan, Hsiao-Chi Hung, I-Tai Chou, Amy S Yee, Chun-Yin Huang
• Journal: Oral oncology (Oral Oncol) Vol. 49 Issue 2 Pg. 129-35 (Feb 2013) ISSN: 1879-0593 [Electronic] England
• PMID: 22944050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

• 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, metabolism)
• Humans
• Male
• Mice
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Invasiveness
• Proto-Oncogene Proteins c-akt (metabolism)
• Repressor Proteins (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)