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....

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Main Authors: Yuchen Ma, Xiaoli Qian, Qun Yu, Yadan Dong, Jiapeng Wang, Heng Liu, Huai Xiao
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/1/123
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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.
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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
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