دورية أكاديمية
Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling
| العنوان: | Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling |
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| المؤلفون: | Ana Carolina B. da C. Rodrigues, Suellen L. R. Silva, Ingrid R. S. B. Dias, Rafaela G. A. Costa, Maiara de S. Oliveira, Milena B. P. Soares, Rosane B. Dias, Ludmila F. Valverde, Clarissa A. G. Rocha, Emily M. Johnson, Cristina Pina, Daniel P. Bezerra |
| المصدر: | Cell Death Discovery, Vol 10, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: | Nature Publishing Group, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| الوصف: | Abstract Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2058-7716 |
| Relation: | https://doaj.org/toc/2058-7716 |
| DOI: | 10.1038/s41420-024-01909-4 |
| URL الوصول: | https://doaj.org/article/45153271df08471280ba301d8a84973f |
| رقم الأكسشن: | edsdoj.45153271df08471280ba301d8a84973f |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20587716 |
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| DOI: | 10.1038/s41420-024-01909-4 |