富含多酚/皂苷的三叶漆提取物通过 PI3K/AKT/mTOR 信号通路对 THP-1 细胞产生凋亡作用。
The polyphenol/saponin-rich Rhus tripartita extract has an apoptotic effect on THP-1 cells through the PI3K/AKT/mTOR signaling pathway.
机构信息
Laboratory of Pastoral Ecosystems and Valorization of Spontaneous Plants and Microorganisms, Institute of Arid Regions (IRA), Tunis, Medenine, Tunisia.
Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Ferrata 9, 27100, Pavia, Italy.
出版信息
BMC Complement Med Ther. 2021 May 27;21(1):153. doi: 10.1186/s12906-021-03328-9.
BACKGROUND
Hyperactivation of mechanistic target of rapamycin (mTOR) signaling pathway is involved in the regulation of cellular growth, proliferation, and more in general, is a common phenomenon in most types of cancers. Thus, natural substances targeting this pathway can be of great therapeutic potential in supporting the treatment of tumor patients. Rhus tripartita (Ucria) Grande is a plant growing in desertic areas which is traditionally used for the treatment of several diseases in Tunisia. In the present work, the biochemical profile of the main compounds present in the plant leaf extract was determined and the anti-leukemic potential of the plant extracts against acute monocytic leukaemia (AML) THP-1 cells was investigated.
METHODS
After HPLC identification of some phenolic compounds present in the plant extract and the quantification of saponin content, the cytotoxic effect of Rhus tripartita extracts on THP-1 cell culture was evaluated using the colorimetric MTT assay for cell viability. THP-1 cells were incubated with medium containing the relative IC concentrations of total plant extract, saponin extract and some standard compounds (rutin (R); kaempferol (K); mixture of catechin, epicatechin, and epicatechin-gallate (CEEG); ellagic acid (EA). Finally, qRT-PCR and western blotting analysis were used to evaluate the effect of some flavonoids present in a crude extract of polyphenols and the total extract of saponins on cell survival and apoptosis.
RESULTS
Analysis of expression level of some gene (PIK3CA, PTEN, AKT1, mTOR, EIF4E, RPS6KB1, and TSC1) involved in the mTOR pathway and the phosphorylation of S6 and AKT proteins allowed to observe that a total Rhus tripartita extract and some of the compounds found in the extract controls THP-1 cell proliferation and apoptosis via regulation of the PI3K-Akt-mTOR signaling pathway.
CONCLUSION
Rhus tripartita-induced inhibition of cell cycle and induction of apoptosis may involve the mTOR pathway. Therefore, Rhus tripartita extract may be a useful candidate as a natural anti-cancer drug to support the treatment of AML.
背景
机械靶标雷帕霉素（mTOR）信号通路的过度激活参与了细胞生长、增殖等的调节，是大多数类型癌症的共同现象。因此，靶向该途径的天然物质在支持肿瘤患者治疗方面具有很大的治疗潜力。漆树（Ucria）是一种生长在沙漠地区的植物，传统上用于治疗突尼斯的几种疾病。在本工作中，确定了植物叶提取物中主要化合物的生化特征，并研究了植物提取物对急性单核细胞白血病（AML）THP-1 细胞的抗白血病潜力。
方法
在 HPLC 鉴定植物提取物中存在的一些酚类化合物并定量皂苷含量后，使用比色 MTT 法评估 Rhus tripartita 提取物对 THP-1 细胞培养的细胞毒性。将 THP-1 细胞与含有相对 IC 浓度的总植物提取物、皂苷提取物和一些标准化合物（芦丁（R）；山奈酚（K）；儿茶素、表儿茶素和表儿茶素没食子酸酯（CEEG）混合物；鞣花酸（EA）的培养基一起孵育。最后，使用 qRT-PCR 和 Western blotting 分析评估多酚粗提物和皂苷总提物中一些类黄酮对细胞存活和凋亡的影响。
结果
分析参与 mTOR 途径的一些基因（PIK3CA、PTEN、AKT1、mTOR、EIF4E、RPS6KB1 和 TSC1）和 S6 和 AKT 蛋白磷酸化的表达水平，观察到总漆树提取物和提取物中的一些化合物控制 THP-1 细胞增殖和凋亡通过调节 PI3K-Akt-mTOR 信号通路。
结论
漆树诱导的细胞周期抑制和凋亡诱导可能涉及 mTOR 途径。因此，漆树提取物可能是一种有用的天然抗癌药物候选物，可用于支持 AML 的治疗。
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