Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages
Inosine (IS) is a naturally occurring metabolite of adenosine with potent immunomodulatory effects. This study investigates the immunomodulatory effects of inosine, particularly its ability to inhibit the development of colorectal cancer (CRC) cells CT26 through modulation of macrophage phenotypes....
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2024-12-01
|
Series: | Molecules |
Subjects: | |
Online Access: | https://www.mdpi.com/1420-3049/30/1/123 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1841549060038721536 |
---|---|
author | Yuchen Ma Xiaoli Qian Qun Yu Yadan Dong Jiapeng Wang Heng Liu Huai Xiao |
author_facet | Yuchen Ma Xiaoli Qian Qun Yu Yadan Dong Jiapeng Wang Heng Liu Huai Xiao |
author_sort | Yuchen Ma |
collection | DOAJ |
description | Inosine (IS) is a naturally occurring metabolite of adenosine with potent immunomodulatory effects. This study investigates the immunomodulatory effects of inosine, particularly its ability to inhibit the development of colorectal cancer (CRC) cells CT26 through modulation of macrophage phenotypes. Aside from the already reported effects of inosine on T cells, in this study, in vitro experiments revealed that inosine could modulate macrophage phenotype. The effects of inosine on the M1/M2 macrophage polarization were investigated at the cellular level. Its role in regulating CRC proliferation and migration was further examined. In addition, a CT26 tumor mouse model was established to assess the mechanism of action of inosine by tumor weight measurement, immunohistochemistry, and immunofluorescence. Inosine significantly increased M1 macrophage markers CD86 and iNOS and enhanced the anti-tumor activity of M1 macrophages, effectively inhibiting CRC progression and metastasis potential. In vivo, inosine had significant tumor inhibitory activity. It also significantly reduced the expression of Ki-67 and promoted the polarization of M1 macrophages. |
format | Article |
id | doaj-art-3b5947ff6cbd4432a53afe89c0e9d0eb |
institution | Kabale University |
issn | 1420-3049 |
language | English |
publishDate | 2024-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Molecules |
spelling | doaj-art-3b5947ff6cbd4432a53afe89c0e9d0eb2025-01-10T13:18:57ZengMDPI AGMolecules1420-30492024-12-0130112310.3390/molecules30010123Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of MacrophagesYuchen Ma0Xiaoli Qian1Qun Yu2Yadan Dong3Jiapeng Wang4Heng Liu5Huai Xiao6Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaYunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, National-Local Joint Engineering Research Center of Entomoceutics, College of Pharmacy, Dali University, Dali 671000, ChinaInosine (IS) is a naturally occurring metabolite of adenosine with potent immunomodulatory effects. This study investigates the immunomodulatory effects of inosine, particularly its ability to inhibit the development of colorectal cancer (CRC) cells CT26 through modulation of macrophage phenotypes. Aside from the already reported effects of inosine on T cells, in this study, in vitro experiments revealed that inosine could modulate macrophage phenotype. The effects of inosine on the M1/M2 macrophage polarization were investigated at the cellular level. Its role in regulating CRC proliferation and migration was further examined. In addition, a CT26 tumor mouse model was established to assess the mechanism of action of inosine by tumor weight measurement, immunohistochemistry, and immunofluorescence. Inosine significantly increased M1 macrophage markers CD86 and iNOS and enhanced the anti-tumor activity of M1 macrophages, effectively inhibiting CRC progression and metastasis potential. In vivo, inosine had significant tumor inhibitory activity. It also significantly reduced the expression of Ki-67 and promoted the polarization of M1 macrophages.https://www.mdpi.com/1420-3049/30/1/123inosinemacrophage polarizationcolorectal cancer |
spellingShingle | Yuchen Ma Xiaoli Qian Qun Yu Yadan Dong Jiapeng Wang Heng Liu Huai Xiao Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages Molecules inosine macrophage polarization colorectal cancer |
title | Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages |
title_full | Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages |
title_fullStr | Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages |
title_full_unstemmed | Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages |
title_short | Inosine Prevents Colorectal Cancer Progression by Inducing M1 Phenotypic Polarization of Macrophages |
title_sort | inosine prevents colorectal cancer progression by inducing m1 phenotypic polarization of macrophages |
topic | inosine macrophage polarization colorectal cancer |
url | https://www.mdpi.com/1420-3049/30/1/123 |
work_keys_str_mv | AT yuchenma inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT xiaoliqian inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT qunyu inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT yadandong inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT jiapengwang inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT hengliu inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages AT huaixiao inosinepreventscolorectalcancerprogressionbyinducingm1phenotypicpolarizationofmacrophages |