Advanced

Montelukast, a CysLT1 receptor antagonist, reduces colon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer

Bellamkonda, Kishan LU ; Satapathy, Shakti Ranjan LU ; Douglas, Desiree LU ; Chandrashekar, Naveenkumar; Selvanesan, Benson Chellakkan LU ; Liu, Minghui LU ; Savari, Sayeh LU ; Jonsson, Gunilla LU and Sjölander, Anita LU (2018) In Cancer Letters 437. p.13-24
Abstract

Inflammation is implicated in the etiology of sporadic colon cancer (CC), which is one of the leading causes of cancer-related deaths worldwide. Here, we report that inhibition of the inflammatory receptor CysLT1 through its antagonist, montelukast, is beneficial in minimizing stemness in CC and thereby minimizing tumor growth in a mouse xenograft model of human colon cancer. Upon treatment with montelukast, colonospheres derived from HT-29 and SW-480 human colon cancer cells exhibited a significant phenotypic change coupled with the downregulation of mRNA and protein expression of cancer stem cell (CSC) markers ALDH1 and DCLK1. Moreover, montelukast reduced the size of HT-29 cell-derived tumors in mice. The reduction in... (More)

Inflammation is implicated in the etiology of sporadic colon cancer (CC), which is one of the leading causes of cancer-related deaths worldwide. Here, we report that inhibition of the inflammatory receptor CysLT1 through its antagonist, montelukast, is beneficial in minimizing stemness in CC and thereby minimizing tumor growth in a mouse xenograft model of human colon cancer. Upon treatment with montelukast, colonospheres derived from HT-29 and SW-480 human colon cancer cells exhibited a significant phenotypic change coupled with the downregulation of mRNA and protein expression of cancer stem cell (CSC) markers ALDH1 and DCLK1. Moreover, montelukast reduced the size of HT-29 cell-derived tumors in mice. The reduction in tumor size was associated with decreased levels of ALDH1A1, DCLK1, BCL2 mRNA and macrophage infiltration into the tumor tissue. Interestingly, this treatment elevated levels of the tumor suppressor 15-PGDH while reducing COX-2 expression. Our data highlight the association of CysLT1R with CSCs and demonstrate that inhibition of CysLT1R could prove beneficial in minimizing CSC-induced tumor growth. This work advances the notion that targeting CSCs is a promising approach to improve outcomes in those afflicted with colon cancer.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ALDH1, Colon cancer, Colon cancer stem cells, CysLT1 receptor, DCLK1, Montelukast
in
Cancer Letters
volume
437
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85052505972
ISSN
0304-3835
DOI
10.1016/j.canlet.2018.08.019
language
English
LU publication?
yes
id
a6cf9d6d-a7cd-4370-b0bf-ab2d9e6889ce
date added to LUP
2018-09-25 07:49:20
date last changed
2019-02-20 11:27:34
@article{a6cf9d6d-a7cd-4370-b0bf-ab2d9e6889ce,
  abstract     = {<p>Inflammation is implicated in the etiology of sporadic colon cancer (CC), which is one of the leading causes of cancer-related deaths worldwide. Here, we report that inhibition of the inflammatory receptor CysLT<sub>1</sub> through its antagonist, montelukast, is beneficial in minimizing stemness in CC and thereby minimizing tumor growth in a mouse xenograft model of human colon cancer. Upon treatment with montelukast, colonospheres derived from HT-29 and SW-480 human colon cancer cells exhibited a significant phenotypic change coupled with the downregulation of mRNA and protein expression of cancer stem cell (CSC) markers ALDH1 and DCLK1. Moreover, montelukast reduced the size of HT-29 cell-derived tumors in mice. The reduction in tumor size was associated with decreased levels of ALDH1A1, DCLK1, BCL2 mRNA and macrophage infiltration into the tumor tissue. Interestingly, this treatment elevated levels of the tumor suppressor 15-PGDH while reducing COX-2 expression. Our data highlight the association of CysLT<sub>1</sub>R with CSCs and demonstrate that inhibition of CysLT<sub>1</sub>R could prove beneficial in minimizing CSC-induced tumor growth. This work advances the notion that targeting CSCs is a promising approach to improve outcomes in those afflicted with colon cancer.</p>},
  author       = {Bellamkonda, Kishan and Satapathy, Shakti Ranjan and Douglas, Desiree and Chandrashekar, Naveenkumar and Selvanesan, Benson Chellakkan and Liu, Minghui and Savari, Sayeh and Jonsson, Gunilla and Sjölander, Anita},
  issn         = {0304-3835},
  keyword      = {ALDH1,Colon cancer,Colon cancer stem cells,CysLT1 receptor,DCLK1,Montelukast},
  language     = {eng},
  month        = {11},
  pages        = {13--24},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Montelukast, a CysLT1 receptor antagonist, reduces colon cancer stemness and tumor burden in a mouse xenograft model of human colon cancer},
  url          = {http://dx.doi.org/10.1016/j.canlet.2018.08.019},
  volume       = {437},
  year         = {2018},
}