ArticleToxicology letters2021
The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells.
Article in Toxicology letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Furin as a Novel Pan-Viral Therapeutic Target: Implications for Dengue and SARS-CoV-2.Viruses · 2026Review
- Genotoxic potential of Dianthus superbus var. superbus and Petasites paradoxus (Retz.) Baumg. methanolic extracts in Chinese hamster ovary cells.Scientific reports · 2026Article
- Current situation and research progress of luteolin in the treatment of gastrointestinal malignant tumors.Discover oncology · 2026Review
- Mechanistic study of pexidartinib-induced toxicity in human hepatic cells.Chemico-biological interactions · 2025Article
- Anti-Oxidant, Anti-Inflammatory and Antiviral Properties of Luteolin Against SARS-CoV-2: Based on Network Pharmacology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Luteolin in Inflammatory Bowel Disease and Colorectal Cancer: A Disease Continuum Perspective.Current issues in molecular biology · 2025Review
- Luteolin Alleviates Inflammation Induced byVeterinary sciences · 2025Article
- Potential anticancer effects and toxicity of flavones luteolin and apigeninJournal of environmental science and health. Part C, Toxicology and carcinogenesis · 2025Review
- Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies.Food science & nutrition · 2025Review
- Exploring the pharmacokinetics, drug-likeness, and toxicological features of anticancer flavonoids: a Boulevard to explore their clinical translational potential.Frontiers in pharmacology · 2025Review
- Luteolin: a natural product with multiple mechanisms for atherosclerosis.Frontiers in pharmacology · 2025Review
- Review
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- Review
- Evaluation of weak genotoxicity of hydroxychloroquine in human TK6 cells.Toxicology letters · 2024Article
- A Comprehensive Review of the Phytochemical Constituents and Bioactivities ofTheScientificWorldJournal · 2024Review
- Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.Metabolites · 2022Review
- The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc.International journal of molecular sciences · 2022Review
- Actein contributes to black cohosh extract-induced genotoxicity in human TK6 cells.Journal of applied toxicology : JAT · 2022Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Luteolin (5,7,3',4'-tetrahydroxyflavone) belongs to the flavone subclass of flavonoids. Luteolin and its glycosides are present in many botanical families, including edible plants, fruits, and vegetables. While the beneficial properties of luteolin have been widely studied, fewer studies have investigated its toxicity. In the present study, using human lymphoblastoid TK6 cells and our newly developed TK6-derived cell lines that each stably express a single human cytochrome P450 (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C18, 2C9, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7), we systematically evaluated luteolin-induced cytotoxicity and genotoxicity, and the role of specific CYPs in the bioactivation of luteolin. Treatments with luteolin for 4-24 h induced cytotoxicity, apoptosis, DNA damage, and chromosome damage in a concentration-dependent manner. Subsequently, we observed that luteolin-induced cytotoxicity and genotoxicity, measured by the high-throughput micronucleus assay, were significantly increased in TK6 cells transduced with CYP1A1 and 1A2. In addition, key apoptosis and DNA damage biomarkers, including cleaved PARP-1, cleaved caspase-3, and phosphorylated histone 2AX (γH2A.X), were all significantly increased in the CYP1A1- and 1A2-expressing cells compared with the empty vector controls. Analysis by LC-MS/MS revealed that TK6 cells biotransformed the majority of luteolin into diosmetin, a less toxic O-methylated flavone, after 24 h; the presence of CYP1A1 and 1A2 partially reversed this process. Altogether, these results indicate that metabolism by CYP1A1 and 1A2 enhanced the toxicity of luteolin in vitro. Our results further support the utility of our TK6 cell system for identification of the specific CYPs responsible for chemical bioactivation and toxicity potential.
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