Park Moon Nyeo, Jeon Hee Won, Rahman Md Ataur, Park Se Sun, Jeong Se Yun, Kim Ki Hyun, Kim Sung-Hoon, Kim Woojin, Kim Bonglee
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
Front Oncol. 2022 Mar 9;12:808174. doi: 10.3389/fonc.2022.808174. eCollection 2022.
Blume (DD), also called dragon's blood, has been used as a traditional Korean medicine, especially for relieving pain caused by wound infection. Recently, it has been described that DD has antibacterial and analgesic effects. In this study, the underlying anticancer effect of DD associated with apoptosis was investigated in acute myeloid leukemia cell lines U937 and THP-1. DD exhibited cytotoxic effects and induced apoptosis in U937 and THP-1 cells. Moreover, DD treatment significantly reduced mitochondrial membrane potential (ΔΨ). The protein expression of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, p-H2A.X, CCAAT/enhancer-binding protein (CHOP), and activating transcription factor 4 was upregulated by DD treatment. Consistently, DD-treated cells had increased reactive oxygen species (ROS) level in a concentration-dependent manner miR-216b activation in association with c-Jun inhibition. N-acetyl-L-cysteine pretreatment reversed the cytotoxic effect of DD treatment as well as prevented ROS accumulation. Collectively, the results of this study suggest that the anticancer effect of DD in AML was mediated by CHOP-dependent apoptosis along with ROS accumulation and included upregulation of miR-216b followed by a decrease in c-Jun.
血竭(DD),也被称为龙血,一直被用作传统的韩国药物,尤其用于缓解伤口感染引起的疼痛。最近,有描述称血竭具有抗菌和镇痛作用。在本研究中,在急性髓系白血病细胞系U937和THP-1中研究了血竭与细胞凋亡相关的潜在抗癌作用。血竭在U937和THP-1细胞中表现出细胞毒性作用并诱导细胞凋亡。此外,血竭处理显著降低了线粒体膜电位(ΔΨ)。血竭处理上调了裂解的聚(ADP-核糖)聚合酶、裂解的半胱天冬酶-3、p-H2A.X、CCAAT/增强子结合蛋白(CHOP)和激活转录因子4的蛋白表达。一致地,经血竭处理的细胞以浓度依赖的方式增加了活性氧(ROS)水平,与c-Jun抑制相关的miR-216b激活。N-乙酰-L-半胱氨酸预处理逆转了血竭处理的细胞毒性作用,并防止了ROS积累。总体而言,本研究结果表明,血竭在急性髓系白血病中的抗癌作用是由CHOP依赖的细胞凋亡以及ROS积累介导的,包括miR-216b上调,随后c-Jun减少。