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Oridonin inhibits aberrant AKT activation in breast cancer.

PMID: 

Oncotarget. 2018 May 8 ;9(35):23878-23889. Epub 2018 Feb 1. PMID: 29844859

Abstract Title: 

Oridonin inhibits aberrant AKT activation in breast cancer.

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-PIK3CA, which expresses mutant PIK3CAand has constitutively active AKT signaling. We found that Oridonin, an extract from, 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 PIK3CA. 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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