Mbaveng Armelle T, Damen Francois, Simo Mpetga James D, Awouafack Maurice D, Tane Pierre, Kuete Victor, Efferth Thomas
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128 Mainz, Germany.
Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Evid Based Complement Alternat Med. 2019 Jul 8;2019:8450158. doi: 10.1155/2019/8450158. eCollection 2019.
The effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of namely, betulinic acid (), glyceryl-1-hexacosanoate (), 7-hydroxy-2-(4-hydroxyphenyl)-4-chromen-4-one (), and 6-hydroxy-2-(4-hydroxyphenyl)-4-chromen-4-one (), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound . The resazurin reduction assay was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed by flow cytometry. Constituents of DCB were isolated by column chromatography. Triterpenoid and flavone had cytotoxic effects towards the 9 tested cancer cell lines with IC values below 50 M. The recorded IC values varied from 7.65 M (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 M (against HepG2 hepatocarcinoma cells) for , 18.90 M (CCRF-CEM leukemia cells) to 88.86 M (against HCT116p53 colon adenocarcinoma cells) for and 0.02 M (against CCRF-CEM cells) to 122.96 M (against CEM/ADR5000 cells) for doxorubicin. DCB induced apoptosis in CCRF-CEM cells mostly mediated by MMP alteration and enhanced ROS production; compound induced apoptosis through caspases activation and MMP alteration and increased ROS production. is an interesting cytotoxic plant and deserves more studies leading to new antineoplastic agents to fight cancer and mostly leukemia.
恶性细胞对细胞毒性药物的耐药性极大地阻碍了抗癌化疗的有效性。在本研究中，对从[植物名称]树皮中分离得到的粗提物（DCB）及其化合物，即桦木酸（）、1 - 二十六烷酸甘油酯（）、7 - 羟基 - 2 -（4 - 羟基苯基）- 4H - 色烯 - 4 - 酮（）和6 - 羟基 - 2 -（4 - 羟基苯基）- 4H - 色烯 - 4 - 酮（）的细胞毒性进行了研究。该研究还扩展到评估DCB和化合物诱导细胞凋亡的方式。采用刃天青还原试验进行细胞毒性研究。通过流式细胞术对细胞周期分布、细胞凋亡、线粒体膜电位（MMP）和活性氧（ROS）进行评估。通过柱色谱法分离DCB的成分。三萜类化合物和黄酮类化合物对9种受试癌细胞系具有细胞毒性作用，IC值低于50 μM。记录的IC值范围为：三萜类化合物对多药耐药的CEM - ADR5000白血病细胞为7.65 μM，对HepG2肝癌细胞为44.17 μM；黄酮类化合物对CCRF - CEM白血病细胞为18.90 μM，对HCT116p53结肠腺癌细胞为88.86 μM；阿霉素对CCRF - CEM细胞为0.02 μM，对CEM/ADR5000细胞为122.96 μM。DCB在CCRF - CEM细胞中诱导细胞凋亡主要通过MMP改变和ROS生成增加介导；化合物通过半胱天冬酶激活、MMP改变和ROS生成增加诱导细胞凋亡。[植物名称]是一种有趣的具有细胞毒性的植物，值得开展更多研究以开发新的抗肿瘤药物来对抗癌症，尤其是白血病。
