A combined therapeutic approach: Parthenolide and vincristine modulate autophagy in B-cell acute lymphoblastic leukemia

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-07-29 DOI:10.1016/j.tice.2025.103057

Elmira Zarei , Sepide Namdari , Farahnaz Zare , Gholamreza Rafiei Dehbidi , Mansoureh Nazari , Gholamhossein Tamaddon , Azadeh Omidkhoda

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引用次数: 0

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.

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一种联合治疗方法：Parthenolide和长春新碱调节b细胞急性淋巴细胞白血病的自噬

parthenolide （PTL）是由parthenium parthenium衍生而来，主要通过抑制NF-κB和调节活性氧而具有抗炎和抗癌作用。本研究探讨了PTL作为b细胞急性淋巴母细胞白血病补充治疗的潜力，重点关注其对Nalm-6细胞系的自噬、凋亡和增殖的影响，以及长春新碱，目的是解决多药耐药等挑战。方法增加PTL和VCR浓度作用于sn -6细胞，测定其IC50值，然后以亚IC50剂量联合处理。流式细胞术检测细胞凋亡，Real-time PCR检测自噬相关基因BECN1、ATG10、LC3和P62的表达变化，免疫印迹法检测LC3蛋白水平。结果PTL和VCR均能抑制Nalm-6细胞的增殖，且呈浓度和时间依赖性，在联合处理时具有协同作用。该组合还增加了细胞凋亡，显著增强了自噬相关基因ATG10、LC3和BECN1的表达，降低了P62的表达。此外，VCR和PTL增加了LC3B-II蛋白水平。综上所述，本研究提示联合治疗可促进自噬和细胞凋亡，提示PTL可能是未来治疗B-ALL的有益辅助化疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.