ArticleBMC biotechnology2020
Development of Caco-2 cells expressing four CYPs via a mammalian artificial chromosome.
Article in BMC biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
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- Emerging advances in intestinal models for in vitro preclinical research.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Biomimetic culture substrates for modelling homeostatic intestinal epithelium in vitro.Nature communications · 2025Article
- Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells.Chemical research in toxicology · 2025Article
- Strategy advancements in placental pharmacokinetics: fromFrontiers in pharmacology · 2025Review
- Translational Utility of Organoid Models for Biomedical Research on Gastrointestinal Diseases.Stem cell reviews and reports · 2024Review
- Investigating nanoplastics toxicity using advanced stem cell-based intestinal and lungFrontiers in toxicology · 2023Review
- Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap.Frontiers in pharmacology · 2022Review
- Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice.Scientific reports · 2021Article
- Highly Efficient Microcell-Mediated Transfer of HACs Containing a Genomic Region of Interest into Mammalian Cells.Current protocols · 2021Article
- Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundOral administration is the most common way to deliver drugs to the systemic circulation or target organs. Orally administered drugs are absorbed in the intestine and metabolized in the intestine and liver. In the early stages of drug development, it is important to predict first-pass metabolism accurately to select candidate drugs with high bioavailability. The Caco-2 cell line derived from colorectal cancer is widely used as an intestinal model to assess drug membrane permeability. However, because the expression of major drug-metabolizing enzymes, such as cytochrome P450 (CYP), is extremely low in Caco-2 cells, it is difficult to predict intestinal metabolism, which is a significant factor in predicting oral drug bioavailability. Previously, we constructed a mouse artificial chromosome vector carrying the CYP (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P450 oxidoreductase (POR) (4CYPs-MAC) genes and increased CYP expression and metabolic activity in HepG2 cells via transfer of this vector.
resultsIn the current study, to improve the Caco-2 cell assay model by taking metabolism into account, we attempted to increase CYP expression by transferring the 4CYPs-MAC into Caco-2 cells. The Caco-2 cells carrying the 4CYPs-MAC showed higher CYP mRNA expression and activity. In addition, high metabolic activity, availability for permeation test, and the potential to assess drug-drug interactions were confirmed.
conclusionsThe established Caco-2 cells with the 4CYPs-MAC are expected to enable more accurate prediction of the absorption and metabolism in the human intestine than parental Caco-2 cells. The mammalian artificial chromosome vector system would provide useful models for drug development.
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Registered trials
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