ArticleScientific reports2016
Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
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- A Moexitecan Magnetic Liposomal Strategy for Ferroptosis-Enhanced Chemotherapy.Pharmaceutics · 2023Article
- Transcriptomic Analysis of CRISPR/Cas9-Mediated PARP1-Knockout Cells under the Influence of Topotecan and TDP1 Inhibitor.International journal of molecular sciences · 2023Article
- Article
- New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1.International journal of molecular sciences · 2021Article
- Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells.Oxidative medicine and cellular longevity · 2018Article
- Gold aggregating gold: A novel nanoparticle biosensor approach for the direct quantification of hepatitis C virus RNA in clinical samples.Biosensors & bioelectronics · 2017Article
- Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach.International journal of molecular sciences · 2017Article
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Camptothecin (CPT), a topoisomerase I (TOP1) inhibitor, exhibits anti-tumor activity against a wide range of tumors. Redundancy of TOP1-mediated repair mechanisms is a major challenge facing the efficiency of TOP1-targetting therapies. This study aims to uncover new TOP1 targeting approaches utilising a selection of natural compounds in the presence or absence of tyrosyl DNA phosphodiesterase I (TDP1); a key TOP1-mediated protein-linked DNA break (PDB) repair enzyme. We identify, isoeugenol, a phenolic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but not proficient cells. Consistent with our cellular data, isoeugenol did not inhibit Tdp1 enzymatic activity in vitro nor it sensitized cells to the PARP1 inhibitor olaparib. However, biochemical analyses suggest that isoeugenol inhibits TDP2 catalytic activity; a pathway that can compensate for the absence of TDP1. Consistent with this, isoeugenol exacerbated etoposide-induced cytotoxicity, which generates TOP2-mediated PDBs for which TDP2 is required for processing. Together, these findings identify isoeugenol as a potential lead compound for developing TDP2 inhibitors and encourage structure-activity relationship studies to shed more light on its utility in drug discovery programs.
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Registered trials
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