ArticleCancer biology & therapy2015
A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells to melphalan treatment.
Article in Cancer biology & therapy, 2015. 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, 35 citations in OpenAlex.
- Article
- TERRA G-quadruplex stabilization as a new therapeutic strategy for multiple myeloma.Journal of experimental & clinical cancer research : CR · 2023Article
- Automated Flow Synthesis of Peptide-PNA Conjugates.ACS central science · 2022Article
- The BLM helicase is a new therapeutic target in multiple myeloma involved in replication stress survival and drug resistance.Frontiers in immunology · 2022Article
- Review
- Novel peptide (RATH) mediated delivery of peptide nucleic acids for antiviral interventions.Applied microbiology and biotechnology · 2021Article
- Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications.Beilstein journal of organic chemistry · 2021Review
- Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.Exploration of targeted anti-tumor therapy · 2021Review
- Potential of Peptide Nucleic Acids in Future Therapeutic Applications.Advanced pharmaceutical bulletin · 2018Review
- Article
- Peptide nucleic acids: Advanced tools for biomedical applications.Journal of biotechnology · 2017Review
- Solid-Phase Synthesis of Difficult Purine-Rich PNAs through Selective Hmb Incorporation: Application to the Total Synthesis of Cell Penetrating Peptide-PNAs.Frontiers in chemistry · 2017Article
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAD51-mediated recombinational repair is elevated in multiple myeloma (MM) and predicts poor prognosis. RAD51 has been targeted to selectively sensitize and/or kill tumor cells. Here, we employed a peptide nucleic acid (PNA) to inhibit RAD51 expression in MM cells. We constructed a PNA complementary to a unique segment of the RAD51 gene promoter, spanning the transcription start site, and conjugated it to a nuclear localization signal (PKKKRKV) to enhance cellular uptake and nuclear delivery without transfection reagents. This synthetic construct, (PNArad51_nls), significantly reduced RAD51 transcripts in MM cells, and markedly reduced the number and intensity of de novo and melphalan-induced nuclear RAD51 foci, while increasing the level of melphalan-induced γH2AX foci. Melphalan alone markedly induced the expression of 5 other genes involved in homologous-recombination repair, yet suppression of RAD51 by PNArad51_nls was sufficient to synergize with melphalan, producing significant synthetic lethality of MM cells in vitro. In a SCID-rab mouse model mimicking the MM bone marrow microenvironment, treatment with PNArad51_nls ± melphalan significantly suppressed tumor growth after 2 weeks, whereas melphalan plus control PNArad4µ_nls was ineffectual. This study highlights the importance of RAD51 in myeloma growth and is the first to demonstrate that anti-RAD51 PNA can potentiate conventional MM chemotherapy.
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