AI Article Synopsis
- Cytochrome P450s, particularly CYP2S1, play a key role in metabolizing various compounds and are implicated in the activation of the anticancer drug 1 AQ4N.
- CYP2S1 is predominantly found in tissues outside the liver and its increased expression in certain tumors is significant for disease treatment.
- The synthetic glucocorticoid dexamethasone (DEX) reduces CYP2S1 expression through the glucocorticoid receptor, with other corticosteroids also being effective, and this process involves histone deacetylase activity.
Article Abstract
Cytochrome P450s are monooxygenase proteins involved in the metabolism of both exogenous and endogenous compounds. CYP2S1 can metabolize eicosanoids in the absence of both NADPH and NADPH cytochrome P450 reductase, and can also activate the anticancer agent 1 AQ4N [1,4-bis{[2-(dimethylamino-N-oxide)ethyl]amino}-5,8-dihydroxy anthracene-9,10-dione]. CYP2S1 is mainly expressed in extrahepatic tissues such as the trachea, lung, stomach, small intestine, spleen, skin, breast, kidney and placenta. Furthermore, increased expression of CYP2S1 occurs in several tumors of epithelial origin, making the characterization of CYP2S1 regulation relevant to the treatment of disease. We report that the synthetic glucocorticoid receptor ligand dexamethasone (DEX) represses CYP2S1 expression. The ED(50) is between 1 nM and 3 nM and maximal repression is reached by 48 h. Other corticosteroids are also effective at repressing CYP2S1. We show that repression by DEX is mediated by the glucocorticoid receptor and requires histone deacetylase activity.
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| http://dx.doi.org/10.1016/j.toxlet.2011.11.020 | DOI Listing |
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