Oridonin inhibits aberrant AKT activation in breast cancer

Oncotarget
Bowen SunQi Wang

Abstract

Aberrant activation of phosphatidylinosito-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) signaling in cancer has led to pursuit of inhibitors for targeting this pathway. However, inhibitors of PI3K and AKT have failed to yield efficacious results without adverse effects. Here, we screened a library containing 441 authenticated traditional chinese medicine (TCM) plant extracts by examining their effect on cell viability of a human mammary epithelial cell line HMEC-PIK3CAH1047R, which expresses mutant PIK3CAH1047R and has constitutively active AKT signaling. We found that Oridonin, an extract from Rabdosia rubescens, reduced cell viability to the greatest extent. Oridonin binds to AKT1 and potentially functions as an ATP-competitive AKT inhibitor. Importantly, Oridonin selectively impaired tumor growth of human breast cancer cells with hyperactivation of PI3K/AKT signaling. Moreover, Oridonin prevented the initiation of mouse mammary tumors driven by PIK3CAH1047R. Our results suggest that Oridonin may serve as a potent and durable therapeutic agent for the treatment of breast cancers with hyperactivation of PI3K/AKT signaling.

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Citations

Aug 1, 2020·Frontiers in Immunology·Shaima'a Hamarsheh, Robert Zeiser
Nov 14, 2020·Journal of Biomolecular Structure & Dynamics·Rohit Karn, Isaac Arnold Emerson

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Methods Mentioned

BETA
nuclear magnetic resonance
myristoylation
surface plasmon resonance
chip
xenografts
xenograft
NMR
chips

Software Mentioned

KODAK Molecular Imaging
BIA evaluation
BIA
BIAevaluation
AutoDock Vina

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