ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2023
Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles.
Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The trial behind it
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Who cites it
7 citing papers in PubMed, 8 citations in OpenAlex.
- Targeting MYCN Degradation by HLB-0532259 Induces Senescence in Retinoblastoma.Investigative ophthalmology & visual science · 2026Article
- Extracellular vesicles in ophthalmology: innovations in diagnosis, therapy, and drug delivery.Molecular biology reports · 2026Review
- Scientometric analysis of extracellular vesicles in vision science (up to 2024).Journal of nanobiotechnology · 2025Review
- Piperlongumine enhances the antitumor efficacy of PD-1 inhibitors by inducing immunogenic cell death in prostate cancer cells.World journal of urology · 2025Article
- Multifaceted Therapeutic Potential of Plant-Derived Exosomes: Immunomodulation, Anticancer, Anti-Aging, Anti-Melanogenesis, Detoxification, and Drug Delivery.Biomolecules · 2025Review
- Piperlongumine regulates genes involved in the skin barrier in epidermal keratinocyte HaCaT cells.Animal cells and systems · 2024Article
- Engineering Strategies of Plant-Derived Exosome-Like Nanovesicles: Current Knowledge and Future Perspectives.International journal of nanomedicine · 2024Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Ocular retinoblastoma malignancies, which develop into metastatic phenotypes, result in poor prognosis and survival for infant and child patients. To improve the prognosis of metastatic retinoblastoma, it is important to identify novel compounds with less toxic side effects and higher therapeutic efficacy compared to existing chemotherapeutics. Piperlongumine (PL), a neuroprotective, plant-derived compound has been explored for its anticancer activities both in vitro and in vivo. Here, we analyze the potential efficacy of PL for metastatic retinoblastoma cell treatment. Our data reveal that PL treatment significantly inhibits cell proliferation in metastatic retinoblastoma Y79 cells compared to the commonly used retinoblastoma chemotherapeutic drugs carboplatin, etoposide, and vincristine. PL treatment also significantly increases cell death compared to treatment with other chemotherapeutic drugs. PL-induced cell-death signaling was associated with significantly higher caspase 3/7 activities and greater loss of mitochondrial membrane potential. PL was also internalized into Y79 cells with an estimated concentration of 0.310pM and expression analysis revealed reduced MYCN oncogene levels. We next examined extracellular vesicles derived from PL-treated Y79 cells. Extracellular vesicles in other cancers are pro-oncogenic, mediating systemic toxicities via the encapsulation of chemotherapeutic drugs. Within metastatic Y79 EV samples, an estimated PL concentration of 0.026pM was detected. PL treatment significantly downregulated Y79 EV cargo of the oncogene MYCN transcript. Interestingly, non-PL-treated Y79 cells incubated with EVs from PL-treated cells exhibited significantly reduced cell growth. These findings indicate that in metastatic Y79 cells, PL exhibits potent anti-proliferation effects and oncogene downregulation. Importantly, PL is also incorporated into extracellular vesicles released from treated metastatic cells with measurable anti-cancer effects on target cells at a distance from the site of primary treatment. The use of PL in the treatment of metastatic retinoblastoma may reduce primary tumor proliferation and inhibit metastatic cancer activity systemically via extracellular vesicle circulation.
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Registered trials
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