Saponins From Paris forrestii (Takht.) H. Li Display Potent Activity Against Acute Myeloid Leukemia by Suppressing the RNF6/AKT/mTOR Signaling Pathway
Lu, Qin1; He, Yuanming2,3; Wang, Yuehu4,5; Gao, Li1; Zheng, Yunjing1; Zhang, Zubin2,3; Cao, Biyin2,3; Wang, Qi6; Mao, Xinliang2,3,6; Hu, Shaoyan1
2018-06-26
发表期刊FRONTIERS IN PHARMACOLOGY
ISSN1663-9812
卷号9
摘要Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia (AML) cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones. TSPf induced more than 40% AML cell apoptosis and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation. In line with these findings, TSPf downregulated pro-survival proteins Mcl-1, Bcl-xL, and Bcl-2 but upregulated the expression of tumor suppressor proteins p53, p27, Bax, and Beclin 1. The AKT/mTOR signaling pathway is frequently overactivated in various AML cells, and TSPf was found to suppress the activation of both AKT and mTOR, but had no effects on their total protein expression. This was further confirmed by the inactivation of 4EBP-1 and p7OS6K, two typical downstream signal molecules in the AKT/mTOR pathway. Moreover, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of TSPf almost fully suppressed tumor growth without gross toxicity. Consistent with the findings in cultured cell lines, TSPf also downregulated RNF6 expression along with inactivated AKT/mTOR signaling in tumor tissues. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity, TSPf could be developed for the treatment of AML.
关键词Tspf Rnf6/akt/mtor Signaling Pathway Acute Myeloid Leukemia Herbal Medicine Saponins Cell Apoptosis Rnf6
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/61424
专题资源植物与生物技术所级重点实验室
作者单位1.Soochow Univ, Childrens Hosp, Dept Hematol & Oncol, Suzhou, Peoples R China
2.Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Neuropsychiat Dis, Suzhou, Peoples R China
3.Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, Key Lab Econ Plants & Biotechnol, Kunming, Yunnan, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, Yunnan Key Lab Wild Plant Resources, Kunming, Yunnan, Peoples R China
6.Guangzhou Univ Chinese Med, Inst Clin Pharmacol, Guangzhou, Guangdong, Peoples R China
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Lu, Qin,He, Yuanming,Wang, Yuehu,et al. Saponins From Paris forrestii (Takht.) H. Li Display Potent Activity Against Acute Myeloid Leukemia by Suppressing the RNF6/AKT/mTOR Signaling Pathway[J]. FRONTIERS IN PHARMACOLOGY,2018,9.
APA Lu, Qin.,He, Yuanming.,Wang, Yuehu.,Gao, Li.,Zheng, Yunjing.,...&Hu, Shaoyan.(2018).Saponins From Paris forrestii (Takht.) H. Li Display Potent Activity Against Acute Myeloid Leukemia by Suppressing the RNF6/AKT/mTOR Signaling Pathway.FRONTIERS IN PHARMACOLOGY,9.
MLA Lu, Qin,et al."Saponins From Paris forrestii (Takht.) H. Li Display Potent Activity Against Acute Myeloid Leukemia by Suppressing the RNF6/AKT/mTOR Signaling Pathway".FRONTIERS IN PHARMACOLOGY 9(2018).
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