A Novel Cytochrome P450 2E1 Inhibitor Q11 Is Effective on Lung Cancer via Regulation of the Inflammatory Microenvironment

Lung cancer is the leading cause of death among all cancers. A persistent chronic inflammatory microenvironment is highly correlated with lung cancer. However, there are no anti-inflammatory agents effective against lung cancer. Cytochrome P450 2E1 (CYP2E1) plays an important role in the inflammatory response. Here, it is found that CYP2E1 is significantly higher in the peritumoral tissue of non-small cell lung cancer (NSCLC) patients and lung tumor growth is significantly impeded in Cyp2e1-/- mice. The novel CYP2E1 inhibitor Q11, 1-(4-methyl-5-thialzolyl) ethenone, is effective in the treatment of lung cancer in mice, which can inhibit cancer cells by changing macrophage polarization rather than directly act on the cancer cells. It is also clarify that the benefit of Q11 may associated with the IL-6/STAT3 and MAPK/ERK pathways. The data demonstrate that CYP2E1 may be a novel inflammatory target and that Q11 is effective on lung cancer by regulation of the inflammatory microenvironment. These findings provide a molecular basis for targeting CYP2E1 and illustrate the potential druggability of the CYP2E1 inhibitor Q11. It is discovered and validated CYP2E1 as a novel inflammatory target in lung cancer by patients and Cyp2e1-/- mice. The novel developed CYP2E1 inhibitor Q11, 1-(4-methyl-5-thialzolyl) ethenone, is effective on lung cancer in mice via regulation of the macrophage polarization in the tumor inflammatory microenvironment.image