Author(s): Jorge, Joana ; Neves, Joana ; Alves, Raquel ; Geraldes, Catarina ; Gonçalves, Ana Cristina ; Sarmento-Ribeiro, Ana Bela
Date: 2023
Persistent ID: https://hdl.handle.net/10316/113139
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): acute lymphoblastic leukemia; multiple myeloma; lymphoma; NF- B; NF- B inhibitors; apoptosis; oxidative stress; Humans; NF-kappa B; Reactive Oxygen Species; Cell Line, Tumor; Apoptosis; I-kappa B Proteins; Sesquiterpenes; Lymphoma
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.
