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Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling

Sci Rep. 2020-06; 
Christian M Garrido, Karen M Henkels, Kristen M Rehl, Hong Liang, Yong Zhou, Jordan U Gutterman, Kwang-Jin Cho
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ORF cDNA Clones/MolecularCloud cDNA of human SMPD1 (GenScript, Cat# OHu18710D), SMPD2 (GenScript, Cat# OHu30447D) Get A Quote

摘要

K-Ras must interact primarily with the plasma membrane (PM) for its biological activity. Therefore, disrupting K-Ras PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we found that avicin G, a family of natural plant-derived triterpenoid saponins from Acacia victoriae, mislocalizes K-Ras from the PM and disrupts PM spatial organization of oncogenic K-Ras and H-Ras by depleting phosphatidylserine (PtdSer) and cholesterol contents, respectively, at the inner PM leaflet. Avicin G also inhibits oncogenic K- and H-Ras signal output and the growth of K-Ras-addicted pancreatic and non-small cell lung cancer cells. We further identified that avicin G perturbs lysosomal activity, and disrup... More

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