Anticancer activities of parthenolide in primary effusion lymphoma preclinical models
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John Wiley and Sons Inc
Abstract
The sesquiterpene lactone parthenolide is a major component of the feverfew medicinal plant, Tanacetum parthenium. Parthenolide has been extensively studied for its anti-inflammatory and anticancer properties in several tumor models. Parthenolide's antitumor activities depend on several mechanisms but it is mainly known as an inhibitor of the nuclear factor-κB (NF-κB) pathway. This pathway is constitutively activated and induces cell survival in primary effusion lymphoma (PEL), a rare aggressive AIDS-related lymphoproliferative disorder that is commonly caused by the human herpesvirus 8 (HHV-8) infection. The aim of this study is to evaluate the targeted effect of Parthenolide both in vitro and in vivo. Herein, parthenolide significantly inhibited cell growth, induced G0/G1 cell cycle arrest, and induced massive apoptosis in PEL cells and ascites. In addition, parthenolide inhibited the NF-ĸB pathway suppressing IĸB phosphorylation and p65 nuclear translocation. It also reduced the expression of the DNA methylase inhibitor (DNMT1). Parthenolide induced HHV-8 lytic gene expression without inhibiting latent viral gene expression. Importantly, DMAPT, the more soluble parthenolide prodrug, promoted delay in ascites development and prolonged the survival of PEL xenograft mice. This study supports the therapeutic use of parthenolide in PEL and encourages its further clinical development. © 2021 Wiley Periodicals LLC
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Apoptosis, Nf-ĸb, Nod/scid mice, Parthenolide, Primary effusion lymphoma, Animals, Antineoplastic agents, phytogenic, Biomarkers, Cell cycle checkpoints, Cell line, tumor, Disease models, animal, Disease susceptibility, Drug evaluation, preclinical, Humans, Lymphoma, primary effusion, Mice, Mice, inbred nod, Mice, scid, Sesquiterpenes, Signal transduction, Xenograft model antitumor assays, Dimethylaminoparthenolide, Dna, Dna (cytosine 5) methyltransferase 1, Histone deacetylase 1, Histone h2ax, I kappa b, Immunoglobulin enhancer binding protein, Messenger rna, Protein bax, Protein bcl 2, Protein p21, Protein p53, Unclassified drug, Antineoplastic agent, Biological marker, Sesquiterpene, Animal cell, Animal experiment, Animal model, Antineoplastic activity, Antiproliferative activity, Article, Ascites, Cell cycle, Cell cycle arrest, Cell cycle g0 phase, Cell cycle g1 phase, Cell death, Cell growth, Cell proliferation, Cell viability, Comparative study, Controlled study, Cytotoxicity, Dna fragmentation, Ex vivo study, Female, Flow cytometry, Gene expression, Immunoblotting, In vitro study, In vivo study, Malignant ascites, Mouse, Mtt assay, Nonhuman, Overall survival, Protein expression, Protein phosphorylation, Treatment interruption, Tunel assay, Upregulation, Western blotting, Animal, Cell cycle checkpoint, Disease model, Disease predisposition, Drug effect, Drug screening, Human, Metabolism, Nonobese diabetic mouse, Preclinical study, Scid mouse, Tumor cell line