Oncotarget

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Oridonin inhibits aberrant AKT activation in breast cancer


2019-05-15

To date pan-or isoform-selective inhibitor of PI3K inhibitors, AKT inhibitors, mTOR inhibitors, and dual PI3K/mTOR inhibitors have not yielded durable or efficacious clinical results, Oridonin offers promise of both increased efficacy and reduced toxicity compared with single PI3K, AKT, or even dual PI3K/mTOR inhibitors.

Dr. Jean J. Zhao from the Harvard Medical School, Boston, MA and the Department of Cancer Biology, Dana-Farber Cancer Institute and Dr. Qi Wang from the Department of Pathology and Laboratory Medicine, at the Medical University of South Carolina, Charleston, SC said "Our results suggest that Oridonin may be of substantial clinical utility in breast cancers with hyperactivation of PI3K/AKT signaling."

The PI3K/AKT signaling pathway is improperly activated in many types of human cancer by RTKs and somatic mutations in specific components of the signaling pathway.

Some inhibitors are designed to inhibit individual isoforms in cancers in which the activation of PI3K/AKT signaling relies on specific isoforms only.

Since feedback signaling has been shown to limit the efficacy of PI3K inhibitors, dual PI3K/mTOR inhibitors have also been developed.

Here, the research team screened a library of authenticated TCM plants containing 441 plants extracts by the cell viability assay in a human mammary epithelial cell line HMEC-PIK3CAH1047R with constitutively activated PI3K and AKT signaling.

Of these, Oridonin, an extract from Rabdosia rubescens, reduced cell viability to the greatest extent.

Oridonin selectively impaired the growth of human breast cancer cells with hyperactivation of AKT signaling in vitro and in vivo.

The Zhao/Wang research team concluded that "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."

Full text - http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=24378&path%5B%5D=76573

Correspondence to - Jean J. Zhao - jean_zhao@dfci.harvard.edu and Qi Wang - wangq@musc.edu

Keywords - TCM plant extracts, oridonin, PI3K/AKT signaling, mammary tumor prevention, tumorigenesis



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