Yucel Burcu, Sonmez Mehmet
a Medical Faculty, Department of Medical Biology , Karadeniz Technical University , Trabzon , Turkey.
b Medical Faculty, Department of Internal Medicine, Division of Hematology , Karadeniz Technical University , Trabzon , Turkey.
Hematology. 2018 Jul;23(6):330-336. doi: 10.1080/10245332.2017.1402454. Epub 2017 Nov 15.
Leukemia is a group of bone marrow cancers and drug resistance is one of the challenges in treatment. Caffeic acid phenethyl ester's (CAPE's) anti-proliferative and apoptotic properties have been reported in leukemia cell lines. However, CAPE's effect on drug resistance and cellular metabolism is still unknown. Thus, in this study, we aimed to explore CAPE's effect on drug resistance and oxidative phosphorylation (oxphos).
Leukemia cell lines NB-4, HL-60, and K562 were treated with CAPE. ATP-based cell viability assay was used. For gene expression studies, RNAs were isolated and reverse transcribed. To investigate CAPE's effect on mitochondrial dysfunction in AML cell lines, we examined oxygen consumption rates (OCRs) in our cell lines.
We found 5 μM CAPE sensitized all cell lines to cytarabine. This similar effect was also observed in the Decitabine-resistant K562 cell line. However, no difference was seen in MDR1 expression upon CAPE treatment in all cell lines. OCR significantly decreased upon CAPE treatment in all cell lines, while the expression of key regulatory glycolytic enzymes increased in K562 and NB-4 cell lines. Expression of STAT3 also changed upon CAPE treatment.
Our results suggested that CAPE alters cellular metabolism by decreasing oxphos and increasing glycolysis in K562 and NB-4 cells. Furthermore, CAPE treatment altered STAT3 expression regarding alterations in oxphos and aerobic glycolysis.
Our results suggest a new property of CAPE, which is oxphos repression, and a presumptive link between altered metabolism and drug resistance.
白血病是一组骨髓癌，耐药性是治疗中的挑战之一。咖啡酸苯乙酯（CAPE）在白血病细胞系中的抗增殖和凋亡特性已有报道。然而，CAPE对耐药性和细胞代谢的影响仍不清楚。因此，在本研究中，我们旨在探讨CAPE对耐药性和氧化磷酸化（oxphos）的影响。
用CAPE处理白血病细胞系NB-4、HL-60和K562。采用基于ATP的细胞活力测定法。对于基因表达研究，分离RNA并进行逆转录。为了研究CAPE对AML细胞系线粒体功能障碍的影响，我们检测了细胞系中的氧消耗率（OCR）。
我们发现5μM CAPE使所有细胞系对阿糖胞苷敏感。在耐地西他滨的K562细胞系中也观察到了类似的效果。然而，在所有细胞系中，CAPE处理后MDR1表达没有差异。所有细胞系在CAPE处理后OCR显著降低，而关键调节糖酵解酶的表达在K562和NB-4细胞系中增加。CAPE处理后STAT3的表达也发生了变化。
我们的结果表明，CAPE通过降低K562和NB-4细胞中的oxphos和增加糖酵解来改变细胞代谢。此外，CAPE处理改变了STAT3的表达，这与oxphos和有氧糖酵解的改变有关。
我们的结果表明CAPE具有一种新特性，即oxphos抑制，以及代谢改变与耐药性之间的推测联系。
