Department of Biochemistry, Faculty of Biology, University of Szczecin, 3c Felczaka St, Szczecin, 71-412, Poland.
Molecular Biology and Biotechnology Center, Faculty of Biology, University of Szczecin, 13 Wąska St, Szczecin, 71-415, Poland.
Phytother Res. 2019 Apr;33(4):1208-1221. doi: 10.1002/ptr.6317. Epub 2019 Mar 5.
The aim of this study was to examine the antitumour effects of plant phenolic acids, gallic acid (GA) and ellagic acid (EA), on human promyelocytic leukaemia sensitive HL60 cell line and its resistant sublines exhibiting two MDR phenotypes: HL60/VINC (overexpressing P-glycoprotein) and HL60/MX2 (characterized by the presence of mutated α isoform of topoisomerase II). Both studied compounds exerted comparable cytotoxic activities towards sensitive HL60 cells and their MDR counterparts. It was also found that GA and EA modulated the cellular level of reactive oxygen species in a dose-dependent and time-dependent manner. Furthermore, it was demonstrated that GA (IC ) and EA (IC and IC ) significantly increased the percentage of sub-G1 subpopulation of all studied leukaemia cells causing oligonucleosomal DNA fragmentation. Both compounds used at IC triggered mainly the apoptotic death of these cells. However, GA had no effect on the activity of caspase-3 as well as caspase-8 in sensitive HL60 cells and their MDR counterparts. In contrast, EA provoked a significant activation of these caspases in all studied leukaemia cells. It was also found that lysosomes were not involved in triggering programmed death of sensitive HL60 and MDR cells by GA and EA.
本研究旨在探讨植物酚酸类物质没食子酸（GA）和鞣花酸（EA）对人早幼粒细胞白血病敏感株 HL60 及其具有两种 MDR 表型的耐药亚系（过表达 P 糖蛋白的 HL60/VINC 和拓扑异构酶 II 突变的 α 同工型表达的 HL60/MX2）的抗肿瘤作用。研究发现，两种化合物对敏感 HL60 细胞及其 MDR 对应物均表现出相当的细胞毒性作用。此外，GA 和 EA 还呈剂量和时间依赖性地调节细胞内活性氧水平。进一步研究表明，GA（IC ）和 EA（IC 和 IC ）显著增加了所有研究白血病细胞的亚 G1 亚群比例，导致核小体 DNA 片段化。这两种化合物在 IC 时均能诱导这些细胞的主要凋亡死亡。然而，GA 对敏感 HL60 细胞及其 MDR 对应物中 caspase-3 和 caspase-8 的活性没有影响。相比之下，EA 能显著激活所有研究的白血病细胞中的这些半胱天冬酶。研究还发现，溶酶体不参与 GA 和 EA 诱导敏感 HL60 和 MDR 细胞程序性死亡。
