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.