Guefack Michel-Gael F, Damen Francois, Mbaveng Armelle T, Tankeo Simplice Beaudelaire, Bitchagno Gabin T M, Çelik İlhami, Simo Mpetga James D, Kuete Victor
Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Department of Chemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Evid Based Complement Alternat Med. 2020 Sep 25;2020:4314807. doi: 10.1155/2020/4314807. eCollection 2020.
The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid () was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (HDCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid (), fridelan-3-one (), 2-hydroxy-5-methoxyxanthone (), norathyriol (), 1,3,5,6-tetrahydroxyxanthone (), betulinic acid (), 3'-hydroxymethyl-2'-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5',6':5,6-(6,8-dihydroxyxanthone)-1',4'-dioxane (), and 3'-hydroxymethyl-2'-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5',6':5,6-(xanthone)-1',4'-dioxane (). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC values ranged from 11.43 g/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75 g/mL (against HCT116 (p53) colon adenocarcinoma cells) for the crude extract HRB. Compounds , , and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC values varying from 14.44 M (against CCRF-CEM leukemia cells) to 44.20 M (against the resistant HCT116 (p53) cells) for and from 38.46 M (against CEM/ADR5000 cells) to 112.27 M (against the resistant HCT116 (p53) cells) for . HRB and compound induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or caspases activation and enhanced ROS production for compound . This study demonstrated that is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy.
全球癌症负担仍然是一个严重问题，在发展中国家，令人震惊的是每八名男性中有一人、每十一名女性中有一人死于癌症。癌细胞的多药耐药性（MDR）阻碍了化疗，使这种情况更加恶化。在本研究中，评估了来自[植物名称]树皮的甲醇提取物（HRB）、馏分（HRBa、HRBb和HRBa1 - 5）以及化合物对一组9种癌细胞系的细胞毒性。还研究了HRB和trichadonic酸（[化合物名称]）的作用方式。采用柱色谱法分离HRB的成分。通过刃天青还原试验（RRA）评估植物提取物和植物化学物质的细胞毒性。使用Caspase - Glo试验评估半胱天冬酶的活性，并通过流式细胞术评估活性氧（ROS）（HDCFH - DA）。从HRB中分离出的植物化学物质有trichadonic酸（[化合物名称]）、羽扇豆-3-酮（[化合物名称]）、2-羟基-5-甲氧基呫吨酮（[化合物名称]）、诺拉替罗（[化合物名称]）、1,3,5,6-四羟基呫吨酮（[化合物名称]）、桦木酸（[化合物名称]）、3'-羟甲基-2'-(4″-羟基-3″,5″-二甲氧基苯基)-5',6':5,6-(6,8-二羟基呫吨酮)-1',4'-二氧六环（[化合物名称]）和3'-羟甲基-2'-(4″-羟基-3″,5″-二甲氧基苯基)-5',6':5,6-(呫吨酮)-1',4'-二氧六环（[化合物名称]）。植物提取物HRB、HRBa、HRBa2 - 4、HRBb和阿霉素对9种受试癌细胞系显示出细胞毒性作用。粗提取物HRB的记录IC值范围为11.43 μg/mL（针对过表达P-糖蛋白（gp）的CEM/ADR5000白血病细胞）至26.75 μg/mL（针对HCT116（p53）结肠腺癌细胞）。化合物[化合物名称]、[化合物名称]和阿霉素对9种受试癌细胞系显示出细胞毒性作用，[化合物名称]的IC值范围为14.44 μM（针对CCRF - CEM白血病细胞）至44.20 μM（针对耐药的HCT116（p53）细胞），[化合物名称]的IC值范围为38.46 μM（针对CEM/ADR5000细胞）至112.27 μM（针对耐药的HCT116（p53）细胞）。HRB和化合物[化合物名称]在CCRF - CEM细胞中诱导凋亡。对于HRB，凋亡过程由增强的ROS产生介导；对于化合物[化合物名称]，凋亡过程由半胱天冬酶激活和增强的ROS产生介导。本研究表明，[植物名称]是细胞毒性植物化学物质如trichadonic酸的潜在来源，可在癌症化疗中进一步开发利用。
