Abstract：
BACKGROUND: Recommendations have been made stating that ethnopharmacological usages such as immune and skin disorders, inflammatory, infectious, parasitic and viral diseases should be taken into account if selecting plants for anticancer screening, since these reflect disease states bearing relevance to cancer or cancer-like symptoms. Cameroonian medicinal plants investigated in this work are traditionally used to treat cancer or ailments with relevance to cancer or cancer-like symptoms.
OBJECTIVE: In this study, 21 methanol extracts from 18 Cameroonian medicinal plants were tested in leukemia CCRF-CEM cells, and the best extracts were further tested on a panel of human cancer cell lines, including various multi-drug-resistant (MDR) phenotypes. Mechanistic studies were performed with the three best extracts.
METHODS: Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic effects of methanol extracts from different plants. Flow cytometry was used to analyze cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of extracts from Curcuma longa rhizomes (CLR), Lycopersicon esculentum leaves (LEL), and Psidium guajava bark (PGB).
RESULTS: In a pre-screening of all extracts, 13 out of 21 (61.9%) had IC50 values below 80 µg/mL. Six of these active extracts displayed IC50 values below 30 µg/mL: Cola pachycarpa leaves (CPL), Curcuma longa rhizomes (CLR), Lycopersicon esculentum leaves, Persea americana bark (PAB), Physalis peruviana twigs (PPT) and Psidium guajava bark (PGB). The best extracts displayed IC50 values from 6.25 µg/mL (against HCT116 p53-/-) to 10.29 µg/mL (towards breast adenocarcinoma MDA-MB-231-BCRP cells) for CLR, from 9.64 µg/mL (against breast adenocarcinoma MDA-MB-231 cells) to 57.74 µg/mL (against HepG2 cells) for LEL and from 1.29 µg/mL (towards CEM/ADR5000 cells) to 62.64 µg/mL (towards MDA-MB-231 cells) for PGB. CLR and PGB induced apoptosis in CCRF-CEM cells via caspases activation, MMP depletion and increase ROS production whilst LEL induced apoptosis mediated by caspases activation and increase ROS production.
CONCLUSIONS: The best botanicals tested were CLR and LEL, which are worth to be explored in more detail to fight cancers including MDR phenotypes.
OBJECTIVE: In this study, 21 methanol extracts from 18 Cameroonian medicinal plants were tested in leukemia CCRF-CEM cells, and the best extracts were further tested on a panel of human cancer cell lines, including various multi-drug-resistant (MDR) phenotypes. Mechanistic studies were performed with the three best extracts.
METHODS: Resazurin reduction assay was used to evaluate cytotoxicity and ferroptotic effects of methanol extracts from different plants. Flow cytometry was used to analyze cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of extracts from Curcuma longa rhizomes (CLR), Lycopersicon esculentum leaves (LEL), and Psidium guajava bark (PGB).
RESULTS: In a pre-screening of all extracts, 13 out of 21 (61.9%) had IC50 values below 80 µg/mL. Six of these active extracts displayed IC50 values below 30 µg/mL: Cola pachycarpa leaves (CPL), Curcuma longa rhizomes (CLR), Lycopersicon esculentum leaves, Persea americana bark (PAB), Physalis peruviana twigs (PPT) and Psidium guajava bark (PGB). The best extracts displayed IC50 values from 6.25 µg/mL (against HCT116 p53-/-) to 10.29 µg/mL (towards breast adenocarcinoma MDA-MB-231-BCRP cells) for CLR, from 9.64 µg/mL (against breast adenocarcinoma MDA-MB-231 cells) to 57.74 µg/mL (against HepG2 cells) for LEL and from 1.29 µg/mL (towards CEM/ADR5000 cells) to 62.64 µg/mL (towards MDA-MB-231 cells) for PGB. CLR and PGB induced apoptosis in CCRF-CEM cells via caspases activation, MMP depletion and increase ROS production whilst LEL induced apoptosis mediated by caspases activation and increase ROS production.
CONCLUSIONS: The best botanicals tested were CLR and LEL, which are worth to be explored in more detail to fight cancers including MDR phenotypes.
摘要：
背景：已提出建议，说明民族药理学用法，如免疫和皮肤病，炎症，传染性,如果选择植物进行抗癌筛选，则应考虑寄生虫病和病毒性疾病，因为这些反映了与癌症或癌症样症状相关的疾病状态。在这项工作中研究的喀麦隆药用植物传统上用于治疗与癌症或癌症样症状相关的癌症或疾病。
目的：在本研究中，在白血病CCRF-CEM细胞中测试了18种喀麦隆药用植物的21种甲醇提取物，最好的提取物在一组人类癌细胞系上进一步测试，包括各种多药耐药（MDR）表型。用三种最好的提取物进行机理研究。
方法：采用Resazurin还原法评价不同植物甲醇提取物的细胞毒性和铁效应。流式细胞术用于分析细胞周期，凋亡，线粒体膜电位（MMP），和姜黄根茎（CLR）提取物的活性氧（ROS），石蒜叶（LEL），和番石榴树皮（PGB）。
结果：在所有提取物的预筛选中，21人中有13人（61.9%）的IC50值低于80μg/mL。这些活性提取物中的六种显示出低于30µg/mL的IC50值：厚皮可乐叶（CPL），姜黄根茎（CLR），石蒜叶，PerseaAmericana树皮（PAB），秘鲁细枝（PPT）和番石榴树皮（PGB）。对于CLR，最佳提取物的IC50值从6.25µg/mL（针对HCT116p53-/-）到10.29µg/mL（针对乳腺癌MDA-MB-231-BCRP细胞），LEL从9.64µg/mL（针对乳腺癌MDA-MB-231细胞）到57.74µg/mL（针对HepG2细胞），PGB从1.29µg/mL（针对CEM/ADR5000细胞）到62.64µg/mL（针对MDA-MB-231细胞）。CLR和PGB通过caspases激活诱导CCRF-CEM细胞凋亡,MMP耗尽并增加ROS产生,而LEL诱导由半胱天冬酶激活介导的细胞凋亡并增加ROS产生。
结论：测试的最佳植物药是CLR和LEL，值得更详细地探索以对抗包括MDR表型在内的癌症。
目的：在本研究中，在白血病CCRF-CEM细胞中测试了18种喀麦隆药用植物的21种甲醇提取物，最好的提取物在一组人类癌细胞系上进一步测试，包括各种多药耐药（MDR）表型。用三种最好的提取物进行机理研究。
方法：采用Resazurin还原法评价不同植物甲醇提取物的细胞毒性和铁效应。流式细胞术用于分析细胞周期，凋亡，线粒体膜电位（MMP），和姜黄根茎（CLR）提取物的活性氧（ROS），石蒜叶（LEL），和番石榴树皮（PGB）。
结果：在所有提取物的预筛选中，21人中有13人（61.9%）的IC50值低于80μg/mL。这些活性提取物中的六种显示出低于30µg/mL的IC50值：厚皮可乐叶（CPL），姜黄根茎（CLR），石蒜叶，PerseaAmericana树皮（PAB），秘鲁细枝（PPT）和番石榴树皮（PGB）。对于CLR，最佳提取物的IC50值从6.25µg/mL（针对HCT116p53-/-）到10.29µg/mL（针对乳腺癌MDA-MB-231-BCRP细胞），LEL从9.64µg/mL（针对乳腺癌MDA-MB-231细胞）到57.74µg/mL（针对HepG2细胞），PGB从1.29µg/mL（针对CEM/ADR5000细胞）到62.64µg/mL（针对MDA-MB-231细胞）。CLR和PGB通过caspases激活诱导CCRF-CEM细胞凋亡,MMP耗尽并增加ROS产生,而LEL诱导由半胱天冬酶激活介导的细胞凋亡并增加ROS产生。
结论：测试的最佳植物药是CLR和LEL，值得更详细地探索以对抗包括MDR表型在内的癌症。
