Dataset Information

Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin.

ABSTRACT:

Objective

The aim of this work was to investigate the immunological effect of MENK by analyzing the protein spectrum and bioinformatics of macrophage RAW264.7, and to explore the relationship between macrophage and ferroptosis.

Result

We employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages and macrophages intervened by MENK. A total of 208 DEPs were identified. Among these, 96 proteins had upregulated expression and 112 proteins had downregulated expression. Proteomic analysis revealed a significant enrichment of DEPs associated with iron metabolism. The identification of hub genes was conducted using KEGG pathway diagrams and protein-protein interaction (PPI) analysis. The hub genes identified in this study include HMOX1 and Ferritin (FTH and FTL). A correlation was established between HMOX1, FTH, and FTL in the GO and KEGG databases. The results of PCR, WB and immunofluorescence showed that MENK downregulated the level of HMOX1 and FTH.

Conclusion

MENK had the potential to become an adjuvant chemotherapy drug by regulating iron metabolism in macrophages, reducing levels of HMOX1 and ferritin. We proposed an innovative research direction on the therapeutic potential of MENK, focusing on the relationship between ferroptosis and macrophage activity.

SUBMITTER: Tian J

PROVIDER: S-EPMC10799539 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin.

Tian Jing J Fu Wenrui W Xie Zifeng Z Zhao Yuanlong Y Yang Haochen H Zhao Jiafan J

Proteome science 20240120 1

<h4>Objective</h4>The aim of this work was to investigate the immunological effect of MENK by analyzing the protein spectrum and bioinformatics of macrophage RAW264.7, and to explore the relationship between macrophage and ferroptosis.<h4>Result</h4>We employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages and macrophages intervened by MENK. A total of 208 DEPs were identified. Among these, 96 proteins had upregulated expression and 112 proteins had ...[more]

PMID: 38245706

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Project description:BackgroundBecause adverse reactions or drug resistance are often found after current chemotherapies for metastatic colorectal cancer (mCRC), new treatments are still in demand. Shenqi Sanjie Granules (SSG), an antitumor compound preparation of traditional Chinese medicine, has been recognized for its ability in clinical practice of oncotherapy. Nevertheless, the precise effects of SSG in colorectal cancer (CRC) and underlying mechanisms through which SSG inhibits CRC remain uncertain. The current study aimed to evaluate the anti-CRC activity of the Chinese herbal compound preparation SSG and investigate the underlying mechanisms of action.Materials and methodsInitially, nine distinct cancer cell lines, including five CRC cell lines, one breast cancer cell line, two lung adenocarcinoma cell lines and one cervical cancer cell line, were used to evaluate the antitumor activity of SSG, and the mouse CRC cell line CT26 were used for further research. In vitro experiments utilizing diverse assays were conducted to assess the inhibitory effects of the SSG on CT26. Furthermore, subcutaneous syngeneic mouse model and AOM (azoxymethane)/DSS (dextran sodium sulfate) induced in-situ colitis-related mouse CRC model were used to evaluate the antitumor potential and biotoxicity of SSG in vivo. To elucidate the underlying molecular mechanisms, transcriptome sequencing and network pharmacology analysis were performed. Meanwhile, verification is carried out with quantitative real-time PCR (qRT-PCR) and flow cytometry (FCM) analysis.ResultsOur in vitro inhibition study showed that SSG could effectively inhibit CRC cell line CT26 growth and metastasis, and induce cell death. Neither of apoptosis inhibitor, necroptosis inhibitor, ferroptosis inhibitor, but the combination of the three diminished SSG-induced cell death, suggesting that multiple cell death pathways were involved. Both the syngeneic CRC model and the in-situ CRC model indicated SSG inhibited CRC in vivo with few toxic side effects. Further mechanistic study suggested SSG treatment activated the ferroptosis pathway, particularly mediated by Hmox1, which was upregulated scores of times. Network pharmacology analysis indicated that the active ingredients of SSG, including Quercetin, Luteolin and Kaempferol were potential components directly upregulated Hmox1 expression.ConclusionsCollectively, our findings indicate that the administration of SSG has the potential to inhibit CRC both in vitro and in vivo. The mechanism by which this compound preparation exerts its action is, at least partly, the induction of ferroptosis through upregulating Hmox-1 by its three active ingredients Quercetin, Luteolin and Kaempferol.

Dataset Information

Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin.

Objective

Result

Conclusion

Publications

Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin.

Similar Datasets

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