Department of Life Science and Biochemical Engineering, Sun Moon University, Asan 31460, Korea.
Department of Pharmaceutical Engineering and Biotechnology, Sun Moon University, Asan 31460, Korea.
Int J Mol Sci. 2021 Apr 20;22(8):4265. doi: 10.3390/ijms22084265.
Leukemia is a type of blood cancer caused by the rapid proliferation of abnormal white blood cells. Currently, several treatment options, including chemotherapy, radiation therapy, and bone marrow transplantation, are used to treat leukemia, but the morbidity and mortality rates of patients with leukemia are still high. Therefore, there is still a need to develop more selective and less toxic drugs for the effective treatment of leukemia. Ampelopsin, also known as dihydromyricetin, is a plant-derived flavonoid that possesses multiple pharmacological functions, including antibacterial, anti-inflammatory, antioxidative, antiangiogenic, and anticancer activities. However, the anticancer effect and mechanism of action of ampelopsin in leukemia remain unclear. In this study, we evaluated the antileukemic effect of ampelopsin against acute promyelocytic HL60 and chronic myelogenous K562 leukemia cells. Ampelopsin significantly inhibited the proliferation of both leukemia cell lines at concentrations that did not affect normal cell viability. Ampelopsin induced cell cycle arrest at the sub-G1 phase in HL60 cells but the S phase in K562 cells. In addition, ampelopsin regulated the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors differently in each leukemia cell. Ampelopsin also induced apoptosis in both leukemia cell lines through nuclear condensation, loss of mitochondrial membrane potential, increase in reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), and regulation of Bcl-2 family members. Furthermore, the antileukemic effect of ampelopsin was associated with the downregulation of AKT and NF-κB signaling pathways. Moreover, ampelopsin suppressed the expression levels of leukemia stemness markers, such as Oct4, Sox2, CD44, and CD133. Taken together, our findings suggest that ampelopsin may be an attractive chemotherapeutic agent against leukemia.
白血病是一种由异常白细胞快速增殖引起的血癌。目前，有几种治疗选择，包括化疗、放射治疗和骨髓移植，用于治疗白血病，但白血病患者的发病率和死亡率仍然很高。因此，仍需要开发更具选择性和更少毒性的药物，以有效治疗白血病。蛇葡萄素，也称为二氢杨梅素，是一种植物来源的类黄酮，具有多种药理作用，包括抗菌、抗炎、抗氧化、抗血管生成和抗癌活性。然而，蛇葡萄素在白血病中的抗癌作用和机制尚不清楚。在这项研究中，我们评估了蛇葡萄素对急性早幼粒细胞 HL60 和慢性髓系 K562 白血病细胞的抗白血病作用。蛇葡萄素在不影响正常细胞活力的浓度下显著抑制两种白血病细胞系的增殖。蛇葡萄素诱导 HL60 细胞的细胞周期停滞在亚 G1 期，但在 K562 细胞中停滞在 S 期。此外，蛇葡萄素在每种白血病细胞中以不同的方式调节细胞周期蛋白、细胞周期蛋白依赖性激酶（CDKs）和 CDK 抑制剂的表达。蛇葡萄素还通过核浓缩、线粒体膜电位丧失、活性氧（ROS）生成增加、半胱天冬酶-9、半胱天冬酶-3 和多聚 ADP-核糖聚合酶（PARP）激活以及 Bcl-2 家族成员的调节，诱导两种白血病细胞凋亡。此外，蛇葡萄素的抗白血病作用与 AKT 和 NF-κB 信号通路的下调有关。此外，蛇葡萄素抑制白血病干细胞标志物的表达水平，如 Oct4、Sox2、CD44 和 CD133。总之，我们的研究结果表明，蛇葡萄素可能是一种有吸引力的治疗白血病的化疗药物。
