Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Sep 24, 2020; 11(9): 732-746
Published online Sep 24, 2020. doi: 10.5306/wjco.v11.i9.732
Diacerein treatment prevents colitis-associated cancer in mice
Daiane S M Paulino, Maria Carolina S Mendes, Juliana A Camargo, Sandra R Brambilla, Tanila Wood Dos Santos, Marcelo L Ribeiro, José Barreto Campello Carvalheira
Daiane S M Paulino, Maria Carolina S Mendes, Juliana A Camargo, Sandra R Brambilla, José Barreto Campello Carvalheira, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Sao Paulo 13083-970, Brazil
Tanila Wood Dos Santos, Marcelo L Ribeiro, Department of Clinical Pharmacology and Gastroenterology, Sao Francisco University, Sao Paulo 12916-900, Brazil
Author contributions: The experiments that involve animals were performed by Paulino DSM, Mendes MCS, Camargo JA, and Brambila SR; The cell assays were performed by Santos TW; The experimental design was performed by Paulino DSM, Mendes MCS, Camargo JA, Santos TW, Ribeiro ML, and Carvalheira JBC; The analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis) were carried out by Paulino DSM and Carvalheira JBC; The manuscript was written by Paulino DSM and Carvalheira JBC, and it was revised by Carvalheira JBC; Carvalheira JBC was the advisor in this study.
Supported by the São Paulo Research Foundation, No. 07607-8/2013; and the National Research Council, No. 150127/2016-2 and No. 306821/2010-9.
Institutional review board statement: This research did not involve humans.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally-accepted principles for the care and use of laboratory animals
Conflict-of-interest statement: Daiane S M Paulino, Maria Carolina S Mendes, Juliana A Camargo, Sandra R Brambila, Tanila W dos Santos, Marcelo L Ribeiro, and José B C Carvalheira declare that they have no conflict of interest. The authors declare to have total responsibility for the content of this manuscript. TRB Pharma Ind Química Farmacêutica LTDA did not influence the results and writing of this manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: José Barreto Campello Carvalheira, MD, PhD, Associate Professor, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Tessália Vieira Camargo, S/N, Sao Paulo 13083-970, Brazil. jbcc@unicamp.br
Received: May 16, 2020
Peer-review started: May 16, 2020
First decision: June 4, 2020
Revised: June 6, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: September 24, 2020
Processing time: 125 Days and 8.2 Hours
ARTICLE HIGHLIGHTS
Research background

Inflammation is a well-established enabling factor for cancer development and provides a framework for the high prevalence of colon cancer in inflammatory bowel disease.

Research motivation

To detect the mechanism whereby diacerein (DAR), an anti-inflammatory drug, acts in the prevention of colitis-associated cancer (CAC).

Research objectives

This study aimed to investigate the effects of DAR on colon inflammation in mice with CAC and evaluate the action of DAR in the development of cancer stem cells (CSCs).

Research methods

The effects of DAR on colon inflammation in mice with CAC were evaluated by inflammatory index, reverse transcription polymerase chain reaction and western blot. Cytokine levels were measured by enzyme-linked immunosorbent assay. Cells assays evaluated the effects of DAR on CSCs. Immunohistochemistry and apoptosis assays were also used to evaluate the effects of DAR on tumorigenesis associated with inflammation.

Research results

DAR treatment reduced colon inflammation as well as the number and size of tumors. Accordingly, DAR treatment was associated with reduced intracellular signals of inflammation in the colon. In addition, DAR treatment was associated with a decrease in colon CSC formation.

Research conclusions

DAR-mediated interleukin-1β suppression attenuates inflammation-induced colon cancer and CSC formation, suggesting that besides reducing colonic inflammation, DAR has a direct effect on the inhibition of colon carcinogenesis.

Research perspectives

The reduction of inflammation, CSC formation and tumorigenesis highlights DAR as a potential candidate for the chemoprevention of CAC.