Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization
Abstract Despite significant advancements in cancer immunotherapy, many patients continue to respond poorly. Novel therapeutic strategies and drugs are urgently needed. Here, we found that CYP2E1 is upregulated in M2 macrophages. The CYP2E1 inhibitor, Q11, could inhibit M2 macrophage polarization, w...
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| Format: | Article |
| Language: | English |
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Springer
2024-12-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03912-1 |
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| author | Cunzhen Zhang Yan Fang Mengxue Guo Liming Tang Yurong Xing Jun Zhou Yuanyuan Guo Yuhan Gu Qiang Wen Na Gao Haiwei Xu Hailing Qiao |
| author_facet | Cunzhen Zhang Yan Fang Mengxue Guo Liming Tang Yurong Xing Jun Zhou Yuanyuan Guo Yuhan Gu Qiang Wen Na Gao Haiwei Xu Hailing Qiao |
| author_sort | Cunzhen Zhang |
| collection | DOAJ |
| description | Abstract Despite significant advancements in cancer immunotherapy, many patients continue to respond poorly. Novel therapeutic strategies and drugs are urgently needed. Here, we found that CYP2E1 is upregulated in M2 macrophages. The CYP2E1 inhibitor, Q11, could inhibit M2 macrophage polarization, while CYP2E1 overexpression could promote it. Increased levels of CYP2E1 and M2 macrophages in the tumor microenvironment of HCC patients correlate with poor prognosis. Q11 could inhibit tumor cells by targeting M2 macrophages rather than directly attacking tumor cells. Both Q11 and Cyp2e1 knockout could effectively suppress tumor growth. Q11 reduces the production of CYP2E1 metabolites ( ±)9(10)-DiHOME and ( ±)12(13)-DiHOME, thus attenuating PPARγ activation and M2 macrophage polarization. In summary, our findings suggest that Q11 could suppress M2 macrophage polarization by modulating the CYP2E1/( ±)9(10)-DiHOME or ( ±)12(13)-DiHOME/PPARγ axis, indicating that CYP2E1 may be a potential therapeutic target for HCC, and its inhibitor Q11 may be a potential drug for the treatment of HCC. |
| format | Article |
| id | doaj-art-25bf74b30e704852835644daf2aaa58d |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-25bf74b30e704852835644daf2aaa58d2025-02-02T12:26:53ZengSpringerCancer Immunology, Immunotherapy1432-08512024-12-0174111410.1007/s00262-024-03912-1Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarizationCunzhen Zhang0Yan Fang1Mengxue Guo2Liming Tang3Yurong Xing4Jun Zhou5Yuanyuan Guo6Yuhan Gu7Qiang Wen8Na Gao9Haiwei Xu10Hailing Qiao11Institute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityThe First Affiliated Hospital of Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversityInstitute of Clinical Pharmacology, Zhengzhou UniversityAbstract Despite significant advancements in cancer immunotherapy, many patients continue to respond poorly. Novel therapeutic strategies and drugs are urgently needed. Here, we found that CYP2E1 is upregulated in M2 macrophages. The CYP2E1 inhibitor, Q11, could inhibit M2 macrophage polarization, while CYP2E1 overexpression could promote it. Increased levels of CYP2E1 and M2 macrophages in the tumor microenvironment of HCC patients correlate with poor prognosis. Q11 could inhibit tumor cells by targeting M2 macrophages rather than directly attacking tumor cells. Both Q11 and Cyp2e1 knockout could effectively suppress tumor growth. Q11 reduces the production of CYP2E1 metabolites ( ±)9(10)-DiHOME and ( ±)12(13)-DiHOME, thus attenuating PPARγ activation and M2 macrophage polarization. In summary, our findings suggest that Q11 could suppress M2 macrophage polarization by modulating the CYP2E1/( ±)9(10)-DiHOME or ( ±)12(13)-DiHOME/PPARγ axis, indicating that CYP2E1 may be a potential therapeutic target for HCC, and its inhibitor Q11 may be a potential drug for the treatment of HCC.https://doi.org/10.1007/s00262-024-03912-1Hepatocellular carcinomaCYP2E1InhibitorM2 macrophageMetabolites |
| spellingShingle | Cunzhen Zhang Yan Fang Mengxue Guo Liming Tang Yurong Xing Jun Zhou Yuanyuan Guo Yuhan Gu Qiang Wen Na Gao Haiwei Xu Hailing Qiao Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization Cancer Immunology, Immunotherapy Hepatocellular carcinoma CYP2E1 Inhibitor M2 macrophage Metabolites |
| title | Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization |
| title_full | Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization |
| title_fullStr | Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization |
| title_full_unstemmed | Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization |
| title_short | Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization |
| title_sort | q11 a cyp2e1 inhibitor exerts anti hepatocellular carcinoma effect by inhibiting m2 macrophage polarization |
| topic | Hepatocellular carcinoma CYP2E1 Inhibitor M2 macrophage Metabolites |
| url | https://doi.org/10.1007/s00262-024-03912-1 |
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