ArticleInternational journal of oncology2017
Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer.
Article in International journal of oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer.Disease markers · 2021Trial
- Current State of Knowledge of the Anticancer Properties of Polyphenolic Compounds from Garlic (Molecules (Basel, Switzerland) · 2026Review
- Discovery and Activity Evaluation of Novel Dibenzoxazepinone Derivatives as Glycogen Phosphorylase Inhibitors.Molecules (Basel, Switzerland) · 2025Article
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- Quercetin-Eudragit® polymer complexes with enhanced loading, solubility, stability, and site-specific targeting.Therapeutic delivery · 2025Article
- Natural Hydroxybenzoic and Hydroxycinnamic Acids Derivatives: Mechanisms of Action and Therapeutic Applications.Antioxidants (Basel, Switzerland) · 2025Review
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- New Insights into Aspirin's Anticancer Activity: The Predominant Role of Its Iron-Chelating Antioxidant Metabolites.Antioxidants (Basel, Switzerland) · 2024Review
- The Puzzle of Aspirin and Iron Deficiency: The Vital Missing Link of the Iron-Chelating Metabolites.International journal of molecular sciences · 2024Review
- Analysis of differences in intestinal flora associated with different BMI status in colorectal cancer patients.Journal of translational medicine · 2024Article
- Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease.iScience · 2023Article
- Indomethacin Induces Spermidine/Spermine-NBiomolecules · 2023Article
- Molecular Effects of Iodine-Biofortified Lettuce in Human Gastrointestinal Cancer Cells.Nutrients · 2022Article
- Development and Validation of an HPLC-UV Method for the Quantification of 4'-Hydroxydiclofenac Using Salicylic Acid: Future Applications for Measurement of In Vitro Drug-Drug Interaction in Rat Liver Microsomes.Molecules (Basel, Switzerland) · 2022Article
- Article
- Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro.Molecules (Basel, Switzerland) · 2021Article
- Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis.Cancers · 2021Review
- Salicylic Acid Biosynthesis and Metabolism: A Divergent Pathway for Plants and Bacteria.Biomolecules · 2021Review
- Effects of potential synbiotic interaction between Lactobacillus rhamnosus GG and salicylic acid on human colon and prostate cancer cells.Archives of microbiology · 2021Article
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Authors and funding
8 authors.
Funding
Abstract
Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and treatment.
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