ArticleNucleic acids research2023
Synergistic binding of actinomycin D and echinomycin to DNA mismatch sites and their combined anti-tumour effects.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Actinomycin Analogs From Streptomyces polyantibioticus S4D258: Structural Elucidation and Antiproliferative Activity Against Triple-Negative Breast Cancer.Chemistry & biodiversity · 2026Article
- Review
- Structural basis for asymmetric bis-intercalator targeting of DNA triplex junctions enabling dual inhibition of topoisomerase I and oncogene transcription.Nucleic acids research · 2026Article
- Stepwise transcription stalling by the anti-cancer drug Actinomycin D and insights into short tandem repeat transcription inhibition.Nature communications · 2026Article
- Targeting Expanded CUG and CTG Repeats as a Therapeutic Approach for Myotonic Dystrophy Type 1 (DM1).ChemMedChem · 2026Review
- Actinomycin D-induced bilateral optic nerve atrophy: a case report.International journal of ophthalmology · 2026Article
- Structural and Functional Insights into Targeting GCCG Sites in the EGFR Promoter by Two DNA Intercalators to Inhibit Breast Cancer Metastasis.Journal of medicinal chemistry · 2025Article
- Alternative Approach to Sequence-Specific Recognition of DNA: Cooperative Stacking of Dication Dimers─Sensitivity to Compound Curvature, Aromatic Structure, and DNA Sequence.ACS chemical biology · 2025Article
- Targeting DNA junction sites by bis-intercalators induces topological changes with potent antitumor effects.Nucleic acids research · 2024Article
- Dual dimeric interactions in the nucleic acid-binding protein Sac10b lead to multiple bridging of double-stranded DNA.Heliyon · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Combination cancer chemotherapy is one of the most useful treatment methods to achieve a synergistic effect and reduce the toxicity of dosing with a single drug. Here, we use a combination of two well-established anticancer DNA intercalators, actinomycin D (ActD) and echinomycin (Echi), to screen their binding capabilities with DNA duplexes containing different mismatches embedded within Watson-Crick base-pairs. We have found that combining ActD and Echi preferentially stabilised thymine-related T:T mismatches. The enhanced stability of the DNA duplex-drug complexes is mainly due to the cooperative binding of the two drugs to the mismatch duplex, with many stacking interactions between the two different drug molecules. Since the repair of thymine-related mismatches is less efficient in mismatch repair (MMR)-deficient cancer cells, we have also demonstrated that the combination of ActD and Echi exhibits enhanced synergistic effects against MMR-deficient HCT116 cells and synergy is maintained in a MMR-related MLH1 gene knockdown in SW620 cells. We further accessed the clinical potential of the two-drug combination approach with a xenograft mouse model of a colorectal MMR-deficient cancer, which has resulted in a significant synergistic anti-tumour effect. The current study provides a novel approach for the development of combination chemotherapy for the treatment of cancers related to DNA-mismatches.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.