Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/113139
Title: Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies
Authors: Jorge, Joana 
Neves, Joana 
Alves, Raquel 
Geraldes, Catarina 
Gonçalves, Ana Cristina 
Sarmento-Ribeiro, Ana Bela 
Keywords: acute lymphoblastic leukemia; multiple myeloma; lymphoma; NF- B; NF- B inhibitors; apoptosis; oxidative stress
Issue Date: 23-May-2023
Publisher: MDPI
Project: The present work was supported by CIMAGO—Center of Investigation on Environment, Genetics and Oncobiology, Faculty of Medicine, University of Coimbra, Portugal (Project 18/12), by the Foundation for Science and Technology (FCT), Portugal (Strategic Projects UID/NEU/04539/2013 and UID/NEU/04539/2019) and COMPETE-FEDER (POCI-01-0145-FEDER-007440). FCT supported Joana Jorge with a Ph.D. grant (SFRH/BD/145531/2019). 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 24
Issue: 11
Abstract: Lymphoid malignancies are a group of highly heterogeneous diseases frequently associated with constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway. Parthenolide is a natural compound used to treat migraines and arthritis and found to act as a potent NF-κB signaling inhibitor. This study evaluated in vitro parthenolide efficacy in lymphoid neoplasms. We assessed parthenolide metabolic activity in NCI-H929 (MM), Farage (GCB-DLBCL), Raji (BL), 697 and KOPN-8 (B-ALL), and CEM and MOLT-4 (T-ALL), by resazurin assay. Cell death, cell cycle, mitochondrial membrane potential (ΔΨmit), reactive oxygen species (ROS) and reduced glutathione (GSH) levels, activated caspase-3, FAS-ligand, and phosphorylated NF-κB p65 were evaluated using flow cytometry. CMYC, TP53, GPX1, and TXRND1 expression levels were assessed using qPCR. Our results showed that parthenolide promoted a metabolic activity decrease in all cell lines in a time-, dose-, and cell-line-dependent manner. The mechanism induced by parthenolide was demonstrated to be cell line dependent. Nonetheless, parthenolide promoted cell death by apoptosis with significant ROS increase (peroxides and superoxide anion) and GSH decrease combined with a ΔΨmit reduction across all studied cell lines. Despite the need to further understand parthenolide mechanisms, parthenolide should be considered as a possible new therapeutic approach for B- and T-lymphoid malignancies.
URI: https://hdl.handle.net/10316/113139
ISSN: 1422-0067
DOI: 10.3390/ijms24119167
Rights: openAccess
Appears in Collections:I&D CIBB - Artigos em Revistas Internacionais
I&D ICBR - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais

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