Ask about this productRelated genes to: CYP1A1 antibody
- Gene:
- CYP1A1 NIH gene
- Name:
- cytochrome P450 family 1 subfamily A member 1
- Previous symbol:
- CYP1
- Synonyms:
- P450DX, P1-450, P450-C, CP11
- Chromosome:
- 15q24.1
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-04-23
Related products to: CYP1A1 antibody
Related articles to: CYP1A1 antibody
- Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor clinical outcomes and limited treatment options. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates xenobiotic metabolism through the induction of many cytochrome P450 enzymes such as CYP1A1. In this study, we investigated three 2-phenyl-imidazo-[1,2-]-pyridine derivates (X19724, X19728, and X15695), previously developed as selective estrogen receptor degraders, for their activity in TNBC cell lines. All three compounds activated AHR-dependent transcriptional activity and exhibited selective cytotoxicity toward MDA-MB-468 cells among a panel of TNBC and nontumorigenic mammary epithelial cell lines. Nonresponsive TNBC cell lines lacked either detectable AHR expression or inducible CYP1A1 expression. In sensitive MDA-MB-468 cells, cytotoxicity was accompanied by membrane permeabilization. Genetic ablation or pharmacological antagonism of AHR, as well as inhibition of CYP1A1 activity, markedly attenuated compound-induced cytotoxicity. Proteomic analysis further revealed enrichment of pathways related to phospholipid synthesis and base excision repair, along with increased abundance of proteins associated with DNA damage responses. Finally, among the three compounds, X15695 exhibited the greatest metabolic stability following incubation with human liver microsomes. Collectively, these findings support a model in which activation of AHR-CYP1A1 axis contributes to selective cytotoxicity in TNBC cells, highlighting this pathway as a potential mechanistic vulnerability that can be exploited by imidazopyridine derivatives. - Source: PubMed
Publication date: 2026/06/16
Lin Lo-WeiBeeman Carley EYang JunEbrahimi ArpaBüchel SimoneGrathwol Christoph WJung NicoleBräse StefanHendrix David AMaier Claudia SCato Andrew C BKolluri Siva K - Cancer risk may be influenced by genetic variation and altered expression of xenobiotic-metabolizing enzymes, yet their role in endometrial cancer remains incompletely understood. This study evaluated the association between four polymorphisms in xenobiotic metabolism-related genes rs1799814, rs3892097, rs72554606, and rs1799930 and the risk of endometrial cancer, and assessed and expression in tumor and control tissues. Genetic association analyses, including multivariate and histology-stratified models, were performed, and gene expression levels were compared between cancer and control tissues. Variants in , , and were significantly associated with an increased risk of endometrial cancer, whereas rs72554606 showed a protective effect, particularly in the dominant model. The strongest association was observed for rs1799930 in additive and recessive models. Expression analysis revealed significantly higher and levels in tumor tissues than in control tissues. Stratified analyses showed generally consistent effects, especially for endometrioid carcinoma, although estimates for the serous subtype were limited by sample size. These findings suggest that polymorphisms and altered expression of xenobiotic-metabolizing genes may contribute to endometrial carcinogenesis. Further studies, including independent validation and analyses of gene-environment interactions, are needed. - Source: PubMed
Publication date: 2026/06/25
Skrzypek MaciejGogolewska MonikaBieńkiewicz AndrzejWójcik-Krowiranda KatarzynaMajsterek IreneuszKabziński Jacek - Clavulanic acid, a β-lactamase inhibitor, is widely co-administered with amoxicillin (as in Augmentin) to treat a broad range of mild-to-moderate bacterial infections by inhibiting β-lactamase enzymes produced by resistant bacterial strains. Despite its therapeutic efficacy, clavulanic acid has been associated with drug-induced liver injury, but the underlying mechanisms for this toxicity remain poorly understood. We investigated the contribution of cytochrome P450 (CYP)-mediated metabolism in relation to clavulanic acid-induced cytotoxicity. A panel of TK6-derived cell lines overexpressing 18 individual CYP isoforms (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1) was employed. Cells were incubated for 24 and 48 h with freshly prepared clavulanic acid (20-1000 µM) in RPMI-1640 medium, and the half-maximal inhibitory concentration (IC₅₀) was determined. Cell growth was more markedly delayed after 48 h of treatment than after 24 h of exposure. Following 48 h of treatment, 13 CYP-overexpressing cell lines showed reduced IC₅₀ values compared with parental TK6 and TK6/vector control cells. The rank order was CYP3A4 ≈ CYP3A7 ≈ CYP1A1 < CYP4A11 ≈ CYP2A13 ≈ CYP2C19 < CYP2B6 ≈ CYP1A2 ≈ CYP2C9 < CYP1B1 ≈ CYP2D6 < CYP2E1 ≈ CYP2C18, with the greatest decrease (~2-fold) observed in TK6/CYP3A4 cells. In contrast, five isoforms (CYP2A6, CYP2A7, CYP2C8, CYP3A5, and CYP4B1) showed IC₅₀ values comparable to controls. To examine further the cytotoxic response, TK6/CYP vector and TK6/CYP3A4 cells were treated for 48 h with equitoxic concentrations of clavulanic acid (0.1×, 0.5×, and 1.0× IC₅₀). The exposures resulted in a significant concentration-dependent reduction in cell viability, accompanied by increased lactate dehydrogenase release, the induction of apoptosis, G₀/G₁ phase arrest, and a concentration-dependent elevation in γH2AX phosphorylation, indicative of DNA damage. In conclusion, CYP enzymes, especially CYP3A4, likely contribute to clavulanate-induced cytotoxicity, with necrosis, cell cycle disruption, and γH2AX-associated apoptosis as key cellular responses. - Source: PubMed
Publication date: 2026/07/15
Fang Jia-LongLi XilinChen SiBeland Frederick A - The swine intestinal microbiota dynamically remodels during development and supports gut homeostasis. However, whether stage-specific microbial shifts, are associated with epithelial development remains poorly understood. Here, longitudinal metagenomic profiling of the swine gut microbiome identified Lactiplantibacillus plantarum as a transiently enriched nursery-stage bacterium positively associated with goblet cell numbers. Dietary supplementation with L. plantarum validated this association, showing increased goblet cell numbers and MUC2 expression in the ileum of nursery piglets. Co-culture with porcine ileum organoids further demonstrated that L. plantarum cell-free supernatant promoted ileal organoid growth and goblet cell differentiation. Integrated untargeted metabolomic analyses of ileal samples and bacterial culture supernatants identified indole-3-lactic acid (ILA) as a potential key microbial metabolite from L. plantarum. Mechanistically, ILA promoted intestinal stem cell proliferation and MUC2 expression, accompanied by increased expression of aryl hydrocarbon receptor (AHR) and its downstream target CYP1A1 in ileal organoids. Consistently, activation of AHR using FICZ increased MUC2 expression, whereas inhibition with CH-223191 suppressed MUC2 expression in ileal organoids. Collectively, these findings uncover a L. plantarum-ILA-AHR signaling axis that promotes intestinal goblet cell differentiation, providing mechanistic insight into microbial metabolite-mediated regulation of epithelial homeostasis during post-weaning period in pigs. - Source: PubMed
Publication date: 2026/07/11
Liu ZiyuWu HaiqinHowe SamanthaZuo BinTian YangWang XiaofanAssress Hailemariam AbrhaShang-Lun Lan RennyMu ChunlongXiao YingpingHuang YanLooper MichaelTsai TsungchengZhao Jiangchao - Hyperlipidemia is a major contributor to atherosclerotic cardiovascular disease, yet effective therapeutic strategies targeting lipid metabolism remain limited. Recent evidence has established brown adipose tissue (BAT) as an endocrine organ that specifically expresses and secretes neuregulin 4 (Nrg4), a key factor in metabolic regulation. However, the mechanism by which Nrg4 controls hepatic lipid metabolism remains unclear. Here, we investigated whether Nrg4 modulates lipid homeostasis via a hepatic Human Epidermal Growth Factor Receptor 4 (ErbB4)-dependent pathway. In hyperlipidemic apolipoprotein E-deficient mice, BAT depletion reduced circulating Nrg4 and worsened dyslipidemia, whereas recombinant Nrg4 reactivated hepatic ErbB4 signaling, alleviated steatosis, improved serum lipid profiles, and reduced atherosclerotic plaques. In AML12 hepatocytes, Nrg4 suppressed palmitate-induced lipid accumulation in an ErbB4-dependent manner. Co-culture experiments further confirmed that activated brown adipocytes protect hepatocytes through secreted Nrg4. Transcriptomic profiling identified cytochrome P450 1A1 (CYP1A1) as one of the most markedly upregulated genes following Nrg4 treatment. Since CYP1A1 is a canonical target of the aryl hydrocarbon receptor (AHR), mechanistic experiments demonstrated that Nrg4 restored the protein expression of ErbB4, AHR, and CYP1A1 that was suppressed by palmitate, and these restorative effects were abolished by ErbB4 knockdown, confirming a novel ErbB4/AHR/CYP1A1 signaling pathway. Collectively, our findings elucidate a novel BAT-liver endocrine pathway through which BAT-derived Nrg4 ameliorates hyperlipidemia and atherosclerosis, identifying a promising therapeutic target for dyslipidemia and its cardiovascular complications. - Source: PubMed
Publication date: 2026/07/08
Yang YulongHu YueWu XiqiuXu ZhianZhao XuanDai MinShi Xiaoyan