Department of Histology, Medical University of Gdansk, Gdansk, Poland.
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
J Physiol Pharmacol. 2019 Dec;70(6). doi: 10.26402/jpp.2019.6.02. Epub 2020 Feb 19.
Resveratrol is a naturally occurring polyphenolic compound present in many plant species and wine. It possesses a wide range of beneficial biological properties including anticancer activity. Resveratrol has been demonstrated to induce both autophagy and apoptosis in several human cancer cell lines. The aim of this study was to investigate whether resveratrol modulates autophagy and apoptosis in MOLT-4 human lymphoblastic leukemia and HL-60 human promyelocytic leukemia cells. Cell viability was evaluated by the neutral red uptake assay. Cell cycle distribution, phosphatidylserine externalization, caspase-3 activation, changes of the mitochondrial membrane potential, intracellular production of reactive oxygen species were evaluated by flow cytometry. LC3-I to LC3-II conversion was examined based on Western blotting and immunofluorescence analyses. The level of p62/SQSTM1 protein and PARP1 cleavage were analyzed by Western blotting. The DNA degradation was assessed by gel electrophoresis. We found that resveratrol is able to modulate autophagy in MOLT-4 and HL-60 cells, as evidenced by the detection of an increased level of LC3-II and p62/SQSTM1 proteins. Moreover, resveratrol induced apoptosis in both cell lines which was associated with phosphatidylserine externalization, disruption of the mitochondrial membrane potential, caspase-3 activation, internucleosomal DNA fragmentation, PARP1 cleavage, chromatin condensation, and fragmentation of cell nuclei. The present study provides evidence that resveratrol can act as an autophagy modulator as well as an apoptosis inducer in MOLT-4 and HL-60 human leukemia cells. Our findings imply that resveratrol can be a promising chemotherapeutic agent in the treatment of leukemia.
白藜芦醇是一种天然存在的多酚化合物，存在于许多植物物种和葡萄酒中。它具有广泛的有益的生物学特性，包括抗癌活性。白藜芦醇已被证明在几种人类癌细胞系中诱导自噬和细胞凋亡。本研究旨在探讨白藜芦醇是否调节 MOLT-4 人急性淋巴细胞白血病和 HL-60 人早幼粒细胞白血病细胞中的自噬和细胞凋亡。细胞活力通过中性红摄取试验评估。细胞周期分布、磷脂酰丝氨酸外翻、半胱天冬酶-3 激活、线粒体膜电位变化、细胞内活性氧的产生通过流式细胞术进行评估。LC3-I 到 LC3-II 的转化通过 Western blot 和免疫荧光分析进行检查。p62/SQSTM1 蛋白和 PARP1 切割的水平通过 Western blot 分析。DNA 降解通过凝胶电泳评估。我们发现白藜芦醇能够调节 MOLT-4 和 HL-60 细胞中的自噬，这表现在 LC3-II 和 p62/SQSTM1 蛋白水平的增加。此外，白藜芦醇诱导两种细胞系的细胞凋亡，这与磷脂酰丝氨酸外翻、线粒体膜电位破坏、半胱天冬酶-3 激活、核小体间 DNA 片段化、PARP1 切割、染色质浓缩和细胞核碎裂有关。本研究提供了证据表明，白藜芦醇可以作为 MOLT-4 和 HL-60 人白血病细胞中的自噬调节剂和凋亡诱导剂。我们的研究结果表明，白藜芦醇可以成为治疗白血病的有前途的化疗药物。
