Ngaffo Carine M N, Tchangna Rodrigue S V, Mbaveng Armelle T, Kamga Justin, Harvey Freya M, Ngadjui Bonaventure T, Bochet Christian G, Kuete Victor
Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
Department of Chemistry, Faculty of Science, University of Yaounde I, Yaounde, Cameroon.
Heliyon. 2020 Nov 2;6(11):e05412. doi: 10.1016/j.heliyon.2020.e05412. eCollection 2020 Nov.
The efficiency of cancer chemotherapy is seriously hampered by the development of resistance of neoplastic cells to cytotoxic agents. In the present investigation, the cytotoxicity of the dichloromethane-methanol (1:1) extract of (ASL), fractions (ASLa-c) from the leaves and isolated compounds: chrysoeriol-7--rutinoside (), luteolin-7--rutinoside (), chrysoeriol-7---glucopyranoside (), Apigenin-7---glucopyranoside (), luteolin-3',4'-dimethoxylether-7---glucoside () and luteolin () was investigated. The study was extended to the assessment of the mode of induction of apoptosis by ASL. The resazurin reduction assay (RRA) was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed by flow cytometry. A caspase-Glo assay was used to evaluate caspase activities. Botanicals ASL, ASLb and ASLc as well as doxorubicin displayed observable IC values towards the nine tested cancer cell lines while ASLa and compounds had selective activities. The IC values ranged from 13.45 μg/mL (in CCRF-CEM leukemia cells) to 33.20 μg/mL (against MDA-MB-231- breast adenocarcinoma cells) for ASL, from 16.42 μg/mL (in CCRF-CEM cells) to 29.64 μg/mL (against MDA-MB-231- cells) for ASLc, and from 22.94 μg/mL (in MDA-MB-231- cells) to 40.19 μg/mL (against HCT116 ( colon adenocarcinoma cells) for ASLb (Table 1), and from 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. ASL induced apoptosis in CCRF-CEM cells, mediated by ROS production. is a good cytotoxic plant and should be further explored to develop an anticancer phytomedicine to combat both sensitive and drug resistant phenotypes.
肿瘤细胞对细胞毒性药物产生耐药性,严重阻碍了癌症化疗的效率。在本研究中,对(ASL)的二氯甲烷 - 甲醇(1:1)提取物、叶片中的馏分(ASLa - c)以及分离出的化合物:芹菜素 - 7 - 芸香糖苷()、木犀草素 - 7 - 芸香糖苷()、芹菜素 - 7 - 吡喃葡萄糖苷()、芹菜素 - 7 - 吡喃葡萄糖苷()、木犀草素 - 3',4'-二甲氧基醚 - 7 - 葡萄糖苷()和木犀草素()的细胞毒性进行了研究。该研究还扩展到评估ASL诱导细胞凋亡的方式。采用刃天青还原试验(RRA)进行细胞毒性研究。通过流式细胞术对细胞周期分布、细胞凋亡和活性氧(ROS)进行评估。使用半胱天冬酶 - Glo检测法评估半胱天冬酶活性。植物提取物ASL、ASLb和ASLc以及阿霉素对九种测试癌细胞系均表现出可观察到的IC值,而ASLa和化合物具有选择性活性。ASL的IC值范围为13.45μg/mL(对CCRF - CEM白血病细胞)至33.20μg/mL(对MDA - MB - 231 - 乳腺腺癌细胞),ASLc的IC值范围为16.42μg/mL(对CCRF - CEM细胞)至29.64μg/mL(对MDA - MB - 231 - 细胞)以及ASLb的IC值范围为22.94μg/mL(对MDA - MB - 231 - 细胞)至40.19μg/mL(对HCT116(结肠腺癌细胞)(表1),阿霉素的IC值范围为0.02μM(对CCRF - CEM细胞)至122.96μM(对CEM/ADR5000细胞)。ASL通过产生ROS介导CCRF - CEM细胞凋亡。ASL是一种良好的细胞毒性植物,应进一步探索以开发一种抗癌植物药来对抗敏感和耐药表型。