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
Qin LuShaoyan Hu

Abstract

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 p70S6K, 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 identifie...Continue Reading

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Citations

May 8, 2019·The Kaohsiung Journal of Medical Sciences·Zi-Ming HuangJia-Li Tao
Jul 31, 2019·Critical Reviews in Analytical Chemistry·Yifei PeiYuanzhong Wang
Mar 23, 2021·Journal of Biochemical and Molecular Toxicology·Qiang PeiRui Liu
Oct 8, 2021·Planta·Yiyang ChenXiaowei Du

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Methods Mentioned

BETA
NMR
flow cytometry
Xenograft
Xenografts

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