| First Author | Song CH | Year | 2020 |
| Journal | Biochem Pharmacol | Volume | 182 |
| Pages | 114279 | PubMed ID | 33068552 |
| Mgi Jnum | J:311827 | Mgi Id | MGI:6780817 |
| Doi | 10.1016/j.bcp.2020.114279 | Citation | Song CH, et al. (2020) 17beta-Estradiol strongly inhibits azoxymethane/dextran sulfate sodium-induced colorectal cancer development in Nrf2 knockout male mice. Biochem Pharmacol 182:114279 |
| abstractText | Nuclear factor erythroid 2-related factor 2 (Nrf2) has dual effects on inflammation and cancer progression depending on the microenvironment. Estrogens have a protective effect on colorectal cancer (CRC) development. The aim of this study was to investigate CRC development in Nrf2 knockout (KO) mice. Azoxymethane (AOM) and dextran sulfate sodium (DSS)-treated wild-type (WT) and Nrf2 KO male mice were sacrificed at weeks 2 and 16 after AOM injection with/without 17beta-estradiol (E2) treatment during week 1. Disease activity index and colon tissue damage at week 2 showed strong attenuation following E2 administration in WT mice but to a lesser extent in Nrf2 KO male mice. At week 16, E2 significantly diminished AOM/DSS-induced adenoma/cancer incidence at distal colon in the Nrf2 KO group, but not in the WT. Furthermore, mRNA or protein levels of NF-kappaB-related mediators (i.e., iNOS, TNF-alpha, and IL-1beta) and Nrf2-related antioxidants (i.e., NQO1 and HO-1) were significantly lower in the Nrf2 KO group regardless of E2 treatment compared to the WT. The expression of estrogen receptor beta (ERbeta) was higher in the Nrf2 KO group than in the WT. In conclusion, estrogen further inhibits CRC by upregulating ERbeta-related alternate pathways in the absence of Nrf2. |
