Faculty Collaboration Database

Dietary diindolylmethane suppresses inflammation-driven lung squamous cell carcinoma in mice. Cancer Prev Res (Phila) 2015 Jan;8(1):77-85

Date

11/19/2014

Pubmed ID

25403850

Pubmed Central ID

PMC4289649

DOI

10.1158/1940-6207.CAPR-14-0245

Scopus ID

2-s2.0-84920837736 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Inflammatory conditions of the lung such as chronic obstructive pulmonary disease (COPD) are known to increase lung cancer risk, particularly lung squamous cell carcinoma (LSCC). In the present study, we developed a mouse model of inflammation-driven LSCC that was induced by N-nitroso-trischloroethylurea (NTCU) and enhanced by lipopolysaccharide (LPS), a potent proinflammatory agent contained in tobacco and tobacco smoke, and determined the chemopreventive effects of BioResponse diindolylmethane (DIM) in the same model. Compared with mice treated with NTCU alone, mice treated with the combination of NTCU and LPS had a 9-fold increase in the number of bronchioles with LSCC. Also, compared with mice treated with LPS alone, mice treated with NTCU plus LPS showed significantly increased expression of the inflammatory cytokines IL1α, IL6, and TNFα (all three increased about 7-fold). Parallel to the increased cytokine gene expression, the NTCU plus LPS-treated group exhibited significantly enhanced activation of NF-κB, STAT3, ERK, p-38, and Akt, expression of p53, COX-2, and Mcl-1, and NF-κB- and STAT3-DNA binding in the lung. Dietary administration of DIM (10 μmol/g diet or 2,460 ppm) to mice treated with NTCU plus LPS reduced the incidence of LSCC by 2-fold, suppressed activation/expression of proinflammatory and procarcinogenic proteins and NF-κB- and STAT3-DNA binding, but not the expression of cytokines and p53. This study highlights the potential significance of our mouse model to identify promising drugs or dietary agents for the chemoprevention of human LSCC and that DIM is a very good candidate for clinical lung cancer chemoprevention trials.

Author List

Song JM, Qian X, Teferi F, Pan J, Wang Y, Kassie F

MESH terms used to index this publication - Major topics in bold

Animals
Carcinoma, Squamous Cell
Carmustine
Cytokines
Diet
Disease Models, Animal
Female
Gene Expression Regulation, Neoplastic
Indoles
Inflammation
Lipopolysaccharides
Lung
Lung Neoplasms
Mice
NF-kappa B