Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany; Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt.
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, Mainz 55128, Germany.
Phytomedicine. 2019 Jun;59:152771. doi: 10.1016/j.phymed.2018.11.031. Epub 2018 Nov 26.
The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells.
We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines.
MATERIAL AND METHODS/STUDY DESIGN: Methylene chloride: methanol (1:1) and methanol: HO (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically.
Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts.
The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.
多药耐药（MDR）表型对癌症患者既定化疗的成功构成重大挑战。我们假设具有新型植物化学物质的细胞毒性药用植物可以克服 MDR 并以与药物敏感细胞相似的功效杀死 MDR 细胞。
我们评估了来自埃及一个尚未开发的生态系统的植物提取物，该生态系统具有不同寻常的气候和营养条件，以评估其对敏感和多药耐药癌细胞系的活性。
材料和方法/研究设计：用二氯甲烷：甲醇（1:1）和甲醇：HO（7:3）从 40 种植物中制备提取物，共得到 76 种具有不同极性化合物的馏分。使用 Resazurin 还原测定法评估这些提取物对五对配对的药物敏感及其耐药细胞系的细胞毒性。流式细胞术和 Western blot 用于确定细胞周期分析、细胞凋亡和自噬。使用分光光度法测量活性氧（ROS）。
从 Withania obtusifolia（WO）、Jasonia candicans（JC）、Centaurea lippii（CL）和 Pulicaria undulata（PU）中提取的提取物是 40 种埃及药用植物中 76 种提取物中最活跃的。它们对药物敏感的 CCRF-CEM 白血病细胞系表现出显著的细胞活力降低，IC 值小于 7μg/ml。在多药耐药的 CEM/ADR5000 细胞中，CL（1.82 倍）和 JC（6.09 倍）对这些提取物表现出较低的交叉耐药程度。其他所有耐药细胞系对这四种提取物均未表现出交叉耐药性。进一步研究了这四种提取物的机制评估。
WO、JC、CL 和 PU 的二氯甲烷：甲醇（1:1）馏分是有前途的细胞毒性提取物，可通过不同的细胞死亡途径用于对抗 MDR 癌细胞。
