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, Dschang, Cameroon.
Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.
J Ethnopharmacol. 2018 Aug 10;222:21-33. doi: 10.1016/j.jep.2018.04.036. Epub 2018 Apr 27.
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.
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.
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).
In a pre-screening of all extracts, 13 out of 21 (61.9%) had IC values below 80 µg/mL. Six of these active extracts displayed IC 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 IC 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.
The best botanicals tested were CLR and LEL, which are worth to be explored in more detail to fight cancers including MDR phenotypes.
有建议指出，如果要进行抗癌筛选，应考虑植物的民族药理学用途，如免疫和皮肤疾病、炎症、感染、寄生虫和病毒疾病，因为这些反映了与癌症或类似癌症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癌症或与癌症或类似癌症症状相关的疾病。
在这项研究中，测试了来自 18 种喀麦隆药用植物的 21 种甲醇提取物在白血病 CCRF-CEM 细胞中的活性，对最佳提取物进行了进一步测试，以评估其对人类癌细胞系的活性，包括各种多药耐药（MDR）表型。对三种最佳提取物进行了机制研究。
使用 Resazurin 还原测定法评估不同植物甲醇提取物的细胞毒性和铁死亡作用。使用流式细胞术分析提取物对姜黄根茎（CLR）、番茄叶（LEL）和番石榴皮（PGB）细胞周期、细胞凋亡、线粒体膜电位（MMP）和活性氧（ROS）的影响。
在所有提取物的预筛选中，21 种提取物中有 13 种（61.9%）的 IC 值低于 80µg/mL。其中 6 种活性提取物的 IC 值低于 30µg/mL：厚叶柯叶（CPL）、姜黄根茎（CLR）、番茄叶、梨果美洲树皮（PAB）、番石榴藤枝（PPT）和番石榴皮（PGB）。最佳提取物的 IC 值范围为 6.25µg/mL（针对 HCT116 p53）至 10.29µg/mL（针对乳腺癌腺癌 MDA-MB-231-BCRP 细胞），CLR 的 IC 值为 9.64µg/mL（针对乳腺癌腺癌 MDA-MB-231 细胞）至 57.74µg/mL（针对 HepG2 细胞），LEL 的 IC 值为 1.29µg/mL（针对 CEM/ADR5000 细胞）至 62.64µg/mL（针对 MDA-MB-231 细胞）。CLR 和 PGB 通过半胱天冬酶激活、MMP 耗竭和增加 ROS 产生诱导 CCRF-CEM 细胞凋亡，而 LEL 通过半胱天冬酶激活和增加 ROS 产生诱导凋亡。
测试的最佳植物药是 CLR 和 LEL，它们值得更详细地探索，以对抗包括 MDR 表型在内的癌症。
