Next Article in Journal
Targeting on Asymmetric Dimethylarginine-Related Nitric Oxide-Reactive Oxygen Species Imbalance to Reprogram the Development of Hypertension
Next Article in Special Issue
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
Previous Article in Journal
Exosomes as miRNA Carriers: Formation–Function–Future
Previous Article in Special Issue
Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessCommunication
Int. J. Mol. Sci. 2016, 17(12), 2017; doi:10.3390/ijms17122017

Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

1
Department of Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA
2
Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
3
Northwestern Medicine, Central DuPage Hospital, Winfield, IL 60190, USA
4
Center for Sleep and Circadian Biology, Northwestern University, Evanston, IL 60208, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Takuji Tanaka and Masahito Shimizu
Received: 27 October 2016 / Revised: 23 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
(This article belongs to the Special Issue Inflammation and Cancer)
View Full-Text   |   Download PDF [1474 KB, uploaded 2 December 2016]   |  

Abstract

Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APC)lox468 mice underwent (a) an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b) an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD) cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2) and 6 (MCP6) histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal)/mMCP2 (intraepithelial) mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota. View Full-Text
Keywords: colon cancer; alcohol; circadian disruption; inflammation; microbiota colon cancer; alcohol; circadian disruption; inflammation; microbiota
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Bishehsari, F.; Saadalla, A.; Khazaie, K.; Engen, P.A.; Voigt, R.M.; Shetuni, B.B.; Forsyth, C.; Shaikh, M.; Vitaterna, M.H.; Turek, F.; Keshavarzian, A. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota. Int. J. Mol. Sci. 2016, 17, 2017.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top