Topical Polyethylene Glycol as a Novel Chemopreventive Agent for Oral Cancer via Targeting of Epidermal Growth Factor Response
Open Access
- 4 June 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (6), e38047
- https://doi.org/10.1371/journal.pone.0038047
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG) has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide) rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall) post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat) without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells) and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis.Keywords
This publication has 43 references indexed in Scilit:
- The Mutational Landscape of Head and Neck Squamous Cell CarcinomaScience, 2011
- Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1Science, 2011
- Epidermal Growth Factor Receptor Expression and Gene Copy Number in the Risk of Oral CancerCancer Prevention Research, 2010
- Phase II Randomized, Placebo-Controlled Trial of Green Tea Extract in Patients with High-Risk Oral Premalignant LesionsCancer Prevention Research, 2009
- Randomized Trial of 13-cis Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral PremalignancyJournal of Clinical Oncology, 2009
- Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and SnailMolecular Cancer Therapeutics, 2008
- Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral LesionsCancer Research, 2008
- TP53Mutations and Survival in Squamous-Cell Carcinoma of the Head and NeckNew England Journal of Medicine, 2007
- Molecular biology of squamous cell carcinoma of the head and neckJournal of Clinical Pathology, 2006