PMID- 25403850
OWN - NLM
STAT- MEDLINE
DCOM- 20151019
LR  - 20181113
IS  - 1940-6215 (Electronic)
IS  - 1940-6207 (Print)
IS  - 1940-6215 (Linking)
VI  - 8
IP  - 1
DP  - 2015 Jan
TI  - Dietary diindolylmethane suppresses inflammation-driven lung squamous cell 
      carcinoma in mice.
PG  - 77-85
LID - 10.1158/1940-6207.CAPR-14-0245 [doi]
AB  - 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 IL1alpha, IL6, and TNFalpha (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-kappaB, 
      STAT3, ERK, p-38, and Akt, expression of p53, COX-2, and Mcl-1, and NF-kappaB- and 
      STAT3-DNA binding in the lung. Dietary administration of DIM (10 mumol/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-kappaB- 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.
CI  - (c)2014 American Association for Cancer Research.
FAU - Song, Jung Min
AU  - Song JM
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
FAU - Qian, Xuemin
AU  - Qian X
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
FAU - Teferi, Fitsum
AU  - Teferi F
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
FAU - Pan, Jing
AU  - Pan J
AD  - Department of Pharmacology and Toxicology and Cancer Center, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Wang, Yian
AU  - Wang Y
AD  - Department of Pharmacology and Toxicology and Cancer Center, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Kassie, Fekadu
AU  - Kassie F
AD  - Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. College 
      of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota. 
      kassi012@umn.edu.
LA  - eng
GR  - R21 CA164235/CA/NCI NIH HHS/United States
GR  - R21CA164235-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141117
PL  - United States
TA  - Cancer Prev Res (Phila)
JT  - Cancer prevention research (Philadelphia, Pa.)
JID - 101479409
RN  - 0 (Cytokines)
RN  - 0 (Indoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (N-nitroso-tris-chloroethylurea)
RN  - 0 (NF-kappa B)
RN  - SSZ9HQT61Z (3,3'-diindolylmethane)
RN  - U68WG3173Y (Carmustine)
SB  - IM
MH  - Animals
MH  - Carcinoma, Squamous Cell/*drug therapy
MH  - Carmustine/analogs & derivatives/chemistry
MH  - Cytokines/metabolism
MH  - Diet
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Indoles/*administration & dosage/chemistry
MH  - Inflammation/*drug therapy
MH  - Lipopolysaccharides/chemistry
MH  - Lung/metabolism
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Mice
MH  - NF-kappa B/metabolism
PMC - PMC4289649
MID - NIHMS643639
COIS- Conflict of Interest Statement: We confirm that there are no known conflicts of 
      interest associated with this publication.
EDAT- 2014/11/19 06:00
MHDA- 2015/10/20 06:00
PMCR- 2016/01/01
CRDT- 2014/11/19 06:00
PHST- 2014/11/19 06:00 [entrez]
PHST- 2014/11/19 06:00 [pubmed]
PHST- 2015/10/20 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 1940-6207.CAPR-14-0245 [pii]
AID - 10.1158/1940-6207.CAPR-14-0245 [doi]
PST - ppublish
SO  - Cancer Prev Res (Phila). 2015 Jan;8(1):77-85. doi: 
      10.1158/1940-6207.CAPR-14-0245. Epub 2014 Nov 17.