Dataset Information

TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization.

ABSTRACT: Studies have shown that epigenetic enzymes such as histone deacetylase (HDAC) are closely related to cancers and that several HDAC inhibitors exert antitumor effects. Studies have further suggested that class IIa HDAC inhibitors are related to immune functions, including immune responses and the expression of chemokines and complement pathway components. TMP195, a selective class IIa HDAC inhibitor, has been reported to be effective against breast cancer. However, the role and mechanism of TMP195 in colorectal cancer remain unknown. In this study, we found that TMP195 significantly reduced the tumor burden in two mouse models of colitis-associated colorectal cancer (CAC) and subcutaneous tumor. Mechanistically, TMP195 decreased the proportion of total macrophages but increased the proportion of M1 macrophages by promoting polarization, resulting in the increased release of inflammatory cytokines. TMP195 had no direct effect on the proliferation of colorectal cancer cells, and its antitumor effect on the colorectal cancer disappeared when macrophages were partly depleted by clodronate liposomes. In addition, TMP195 enhanced the efficacy of PD-1 blockade. The present study revealed that the combination of TMP195 and PD-1 blockade may provide a therapeutic strategy for colorectal cancer.

SUBMITTER: Han Y

PROVIDER: S-EPMC9576521 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization.

Han Yicheng Y Sun Jiachun J Yang Yanyan Y Liu Yunlong Y Lou Jun J Pan Hongming H Yao Junlin J Han Weidong W

International journal of biological sciences 20220906 15

Studies have shown that epigenetic enzymes such as histone deacetylase (HDAC) are closely related to cancers and that several HDAC inhibitors exert antitumor effects. Studies have further suggested that class IIa HDAC inhibitors are related to immune functions, including immune responses and the expression of chemokines and complement pathway components. TMP195, a selective class IIa HDAC inhibitor, has been reported to be effective against breast cancer. However, the role and mechanism of TMP19 ...[more]

PMID: 36263186

Similar Datasets

Project description:BackgroundThe mitochondrial dysfunction and oxidative stress imbalance caused by macrophage polarization play a role in the progression of COPD, with CDGSH iron-sulfur domain-containing protein 1 (CISD1) playing a key role. This study revealed the role and mechanism of CISD1 in smoke-induced macrophages.MethodsUsing a pure cigarette smoke exposure-induced COPD mouse model, stimulation of Raw264.7 macrophages with cigarette smoke extract mimics the COPD environment. Knocking down CISD1 expression in macrophages and combining it with high-throughput sequencing to obtain subsequent differentially expressed genes and pathways. Macrophage polarization tendency under different treatments was determined using flow cytometry. Meanwhile, Mitosox, JC-1, DCFH-DA fluorescence intensity was measured to detect mitochondrial function and cellular oxidative stress levels. Western Blot technique was employed to validate autophagy (mitochondrial autophagy) pathway-related proteins. In addition, Elisa technique was used to measure inflammatory factors (IL-6, TNF-a) in the cell supernatant after co-culturing macrophages (Raw264.7) with epithelial cells (MLE12).ResultsCISD1 is underexpressed in peripheral blood monocytes of COPD patients. Under in vitro conditions, we verified that cigarette smoke (smoke extract) indeed inhibits CISD1 expression in macrophages. Subsequently, we found that macrophages with knocked-down CISD1 tend to polarize towards M1 phenotype, and exhibit signs of mitochondrial dysfunction and oxidative stress imbalance. In addition, we observed significant activation of the autophagy pathway in CISD1-inhibited macrophages, with upregulation of LC3A/B and downregulation of p62 protein, as well as increased expression of mitochondrial autophagy-related proteins (PINK1, PARKN). Furthermore, co-culturing CISD1-knockdown macrophages (Raw264.7) with epithelial cells (MLE12) resulted in upregulation of inflammatory factors in the supernatant.ConclusionsSmoke-induced reduction of CISD1 in macrophages promotes M1 polarization and mitochondrial dysfunction by activating the autophagy pathway, thereby promoting the occurrence and development of COPD.

Dataset Information

TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization.

Publications

TMP195 Exerts Antitumor Effects on Colorectal Cancer by Promoting M1 Macrophages Polarization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets