Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2020-11-27 , DOI: 10.1016/j.jep.2020.113632 Armelle T Mbaveng 1 , Godloves F Chi 2 , Idrios N Bonsou 3 , Japheth O Ombito 4 , Samuel O Yeboah 4 , Victor Kuete 1 , Thomas Efferth 5
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Ethnopharmacological relevance
Tetrapleura tetraptera is an African medicinal spice used in traditional medicine to treat several ailments including cancer.
Aim of the study
The present study was designed to evaluate the cytotoxicity of the dichloromethane-methanol (1:1) extract of the fruits of Tetrapleura tetraptera (TTF) and its constituents: (3R, 4S)-3,4-dimethyloxetan-2-one (1), luteolin (2), stigmasterol (4), 3-O-[6′-O-undecanoyl-β-D-glucopyranosyl]stigmasterol (6), olean-12-en-3-β-O-D-glucopyranoside (7), 3-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosylurs-12-en-28-oic acid (8), 3-O-β-D-glucopyranosyl-(1 → 3)-β-D-glucopyranosyl-27-hydroxyolean-12-ene-28-oic acid (9), methyl-O-β-D-glucopyranoside (10), β-D-fructofuranosyl-(2 → 1)-β-D-glucopyranoside (11) towards a panel of cancer cell lines including MDR phenotypes. The cellular mode of induction of apoptosis by TTF and compound 7 was further investigated.
Materials and methods
The resazurin reduction assay (RRA) was applied to determine the cytotoxicity of the studied samples. The cell cycle (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1) and reactive oxygen species (ROS; H2DCFH-DA) were measured by flow cytometry. Column chromatography was used for the purification of TTF, whilst nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation.
Results
The botanical, TTF and the phytochemicals, 2, 7, 8 and 9 as well as doxorubicin exerted cytotoxicity against 9 cancer cell lines including drug-sensitive and drug resistant phenotypes. TTF, compound 7 and doxorubicin were the most active samples, and displayed IC50 values ranging from 10.27 μg/mL (in CCRF-CEM leukemia cells) to 23.61 μg/mL (against HCT116 p53−/− colon adenocarcinoma cells) for TTF, from 4.76 μM (against CCRF-CEM cells) to 12.92 μM (against HepG2 hepatocarcinoma cells) for compound 7, and from 0.02 μM (against CCRF-CEM cells) to 122.96 μM (against CEM/ADR5000 cells) for doxorubicin. TTF induced apoptosis in CCRF-CEM cells through MMP alteration and increased ROS production while compound 7 induced apoptosis mediated by caspases activation, MMP alteration and increased ROS production.
Conclusion
Tetrapleura tetraptera and some of its constituents, mostly compound 7 are good cytotoxic natural products that should be explored in depth to develop new drugs to fight cancers.
中文翻译：
四翅果粗提物中的细胞毒性植物化学物质对多因素耐药癌细胞
民族药理学相关性
Tetrapleura tetraptera是一种非洲药用香料，在传统医学中用于治疗包括癌症在内的多种疾病。
研究目的
本研究旨在评估四翅果(TTF) 果实的二氯甲烷-甲醇 (1:1) 提取物及其成分 (3 R , 4 S )-3,4-二甲基氧杂环丁烷-2-酮的细胞毒性。 ( 1 )、木犀草素(2 )、豆甾醇 ( 4 )、3- O -[6′- O -十一烷酰基- β - D -吡喃葡萄糖基]豆甾醇 ( 6 )、olean-12-en-3- β - O - D -吡喃葡萄糖苷 ( 7 )，3- O - β - D -吡喃葡萄糖基-(1 → 6)- β - D -吡喃葡萄糖基-12-en-28-油酸 ( 8 )，3- O - β -D -吡喃葡萄糖基- (1→3) -β - D-吡喃葡萄糖基-27-羟基齐墩果酸-12-烯-28-油酸( 9 )，甲基-O - β - D-吡喃葡萄糖苷( 10 )， β - D-呋喃果糖基-(2→ 1) -β - D-吡喃葡萄糖苷 ( 11 ) 针对一组包括 MDR 表型的癌细胞系。进一步研究了TTF和化合物7诱导细胞凋亡的细胞模式。
材料和方法
应用刃天青还原测定（RRA）来确定所研究样品的细胞毒性。通过流式细胞术测量细胞周期（PI染色）、细胞凋亡（膜联蛋白V/PI染色）、线粒体膜电位（MMP；JC-1）和活性氧（ROS；H 2 DCFH-DA）。柱色谱用于TTF的纯化，而核磁共振（NMR）光谱分析用于结构阐明。
结果
植物、TTF 和植物化学物质2 、 7 、 8和9以及阿霉素对 9 种癌细胞系（包括药物敏感和耐药表型）发挥细胞毒性。 TTF、化合物7和阿霉素是最活跃的样品，TTF的IC 50值范围为10.27 μg/mL（在CCRF-CEM白血病细胞中）至23.61 μg/mL（针对HCT116 p53 -/−结肠腺癌细胞），对于化合物7 ，从4.76μM（针对CCRF-CEM细胞）至12.92μM（针对HepG2肝癌细胞），以及对于阿霉素从0.02μM（针对CCRF-CEM细胞）至122.96μM（针对CEM/ADR5000细胞）。 TTF 通过 MMP 改变和增加 ROS 产生诱导 CCRF-CEM 细胞凋亡，而化合物7通过半胱天冬酶激活、MMP 改变和增加 ROS 产生介导细胞凋亡。
结论
Tetrapleura tetraptera及其一些成分（主要是化合物7）是良好的细胞毒性天然产物，应深入探索以开发抗癌新药。
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