A Combined Therapeutic Approach: Parthenolide and Vincristine Modulate Autophagy in B-Cell Acute Lymphoblastic Leukemia Publisher



E Zarei ELMIRA ; S Namdari SEPIDE ; F Zare FARAHNAZ ; Gr Dehbidi Gholamreza RAFIEI ; Mv Nazari Mansoureh VISHKAEI ; Gh Tamadon Gholam HOSSEIN ; A Omidkhoda AZADEH
Source: Tissue and Cell Published:2025

Abstract

Background: Parthenolide (PTL), derived from Tanacetum parthenium, is known for its anti-inflammatory and anti-cancer properties, primarily through NF-κB inhibition and modulation of reactive oxygen species. This study investigates PTL's potential as a complementary treatment for B-Cell Acute Lymphoblastic Leukemia, focusing on its effects on autophagy, apoptosis, and proliferation in the Nalm-6 cell line, alongside vincristine, with the aim of addressing challenges such as multi-drug resistance. Methods: Nalm-6 cells were treated with increasing concentrations of PTL and VCR to determine their IC50 values, followed by combination treatments with sub-IC50 doses. Apoptosis was assessed using flow cytometry, while changes in autophagy-related gene expression (BECN1, ATG10, LC3, and P62) were measured via Real-time PCR, and LC3 protein levels were analyzed through Immunoblotting. Results: The results revealed that both PTL and VCR inhibited Nalm-6 cell proliferation in a concentration and time-dependent manner, with a synergistic effect observed in combined treatments. This combination also increased apoptosis and significantly enhanced the expression of autophagy-related genes ATG10, LC3 and BECN1 while decreasing P62 expression. Additionally, VCR and PTL increased LC3B-II protein levels. Conclusion: Overall, the study indicates that combined treatment promotes autophagy and apoptosis, suggesting that PTL could be a beneficial adjunct to chemotherapy for treating B-ALL in the future. © 2025 Elsevier B.V., All rights reserved.