The cytochrome P450 superfamily (CYPs) is a group of metabolic enzymes involved in drug biotransformation/metabolism. It is the most important drug metabolic enzyme; however, its mechanism of action remains unclear.We investigated the expression of CYP2B6 in HeLa cells induced by interleukin-6 (IL-6) and explored the relationship between differentially expressed chondrocytes 1 (DEC1) and CYP2B6 via luciferase reporter, chromatin immunoprecipitation (ChIP) and ELISA assays.We observed the expression of CYP2B6 in HeLa cells exhibited a time-dependent decrease under the effect of IL-6, and the expression of CYP2B6 down-regulated by IL-6was negatively correlated with DEC1. After overexpression or knockdown of DEC1 in HeLa cells, the expression of CYP2B6 decreased or increased. The luciferase reporter assay and ChIP assay confirmed that DEC1 inhibited the expression of CYP2B6 by binding to the CYP2B6 promoter. ELISA results showed that high expression of DEC1 or low expression of CYP2B6 can promote the secretion of IL-6 in HeLa cells, and the secreted IL-6 can continually downregulate the expression of CYP2B6 in HeLa cells.Our results indicate that DEC1/CYP2B6 pathway in the inflammatory environment of tumours, and this provides a small amount of theoretical basis for the study of genes encoding drug-metabolising enzymes.
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http://dx.doi.org/10.1080/00498254.2021.2004335 | DOI Listing |
Yakugaku Zasshi
January 2025
Department of Personalized Medicine and Preventive Healthcare Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.
Notable advances have recently been achieved in drug therapies for renal cell carcinoma (RCC). Several tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have been approved for metastatic RCC (mRCC). The current first-line treatment for mRCC involves combination therapies using TKIs and ICIs.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo, Kyoto 606-8501, Japan. Electronic address:
Eur J Pharm Sci
December 2024
Center of Clinical Pharmacology, the Third Xiangya Hospital, Central South University, China. Electronic address:
Background: Genetic variants in absorption, distribution, metabolism, and excretion (ADME) genes affect drug efficacy and side effects. Whole-exome sequencing (WES) effectively identifies these variants. Findings from Western populations may not apply to the Han Chinese population due to ethnic differences.
View Article and Find Full Text PDFToxicology
December 2024
Department of Toxicology, School of Public Health (Guangdong Provincial Key Laboratory of Tropical Disease Research), Southern Medical University, 1023 S. Shatai Road, Guangzhou 510515, China. Electronic address:
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants, of which BDE-47 could be activated by human cytochrome P450s (CYPs) for chromosome-damaging effects. However, the metabolic activation and mutagenicity of other PBDEs remain unknown. In this study, 14 representative PBDEs were analyzed by molecular docking as potential substrates for several human CYPs.
View Article and Find Full Text PDFRegul Toxicol Pharmacol
December 2024
National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, 72079, USA. Electronic address:
Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N-nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!