Department of Pharmacology, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.
College of Pharmacy, Kyungsung University, Busan, 48434, Republic of Korea.
Sci Rep. 2022 May 7;12(1):7519. doi: 10.1038/s41598-022-11543-8.
Several derivatives derived from the oxime structure have been reported as potential anticancer agents in various cancers. Here, we first tested a novel oxime-containing derivative of 2-((2,4,5-trifluorobenzyl)oxy)benzaldehyde oxime (TFOBO) to evaluate its anticancer effect in myeloid leukemic cells. Compared to (2-((2,4,5-trifluorobenzyl)oxy)phenyl)methanol (TFOPM), the oxime derivative TFOBO suppresses leukemic cell growth by significantly increasing reactive oxygen species (ROS) levels and cell death. Leukemic cells treated with TFOBO displayed apoptotic cell death, as indicated by nuclear condensation, DNA fragmentation, and annexin V staining. TFOBO increases Bax/Bcl2 levels, caspase9, and caspase3/7 activity and decreases mitochondrial membrane potential. ROS production was reduced by N-acetyl-L-cysteine, a ROS scavenger, diphenyleneiodonium chloride, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, after exogenous TFOBO treatment. ROS inhibitors protect leukemic cells from TFOBO-induced cell death. Thus, our study findings suggest that TFOBO promotes apoptosis by modulating ROS and regulating NADPH oxidase activity. Collectively, the oxime-containing derivative TFOBO is a novel therapeutic drug for myeloid leukemia.
几种衍生自肟结构的化合物已被报道在各种癌症中作为潜在的抗癌剂。在这里，我们首次测试了一种新型的肟类化合物 2-((2,4,5-三氟苄基)氧基)苯甲醛肟（TFOBO），以评估其在髓系白血病细胞中的抗癌作用。与肟衍生物 TFOBO 相比，（2-((2,4,5-三氟苄基)氧基)苯基）甲醇（TFOPM）通过显著增加活性氧（ROS）水平和细胞死亡来抑制白血病细胞生长。用 TFOBO 处理的白血病细胞显示出凋亡细胞死亡，如核浓缩、DNA 片段化和膜联蛋白 V 染色所示。TFOBO 增加 Bax/Bcl2 水平、caspase9 和 caspase3/7 活性，降低线粒体膜电位。在 TFOBO 处理后，ROS 清除剂 N-乙酰-L-半胱氨酸和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂二苯并碘鎓氯化物降低了 ROS 产生。ROS 抑制剂可保护白血病细胞免受 TFOBO 诱导的细胞死亡。因此，我们的研究结果表明，TFOBO 通过调节 ROS 和调节 NADPH 氧化酶活性来促进细胞凋亡。总之，含肟的衍生物 TFOBO 是一种治疗髓系白血病的新型治疗药物。
