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Cancer Prev Res (Phila). 2019 Sep 25. pii: canprevres.0244.2019. doi: 10.1158/1940-6207.CAPR-19-0244. [Epub ahead of print]

Scutellarin suppresses patient-derived xenograft tumor growth by directly targeting AKT in esophageal squamous cell carcinoma.

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China-US(Henan) Hormel Cancer Institute.
China-US (Henan) Hormel Cancer Institute.
The Hormel Institute, University of Minnesota.
China-US(Henan) Hormel Cancer Institute


Scutellarin is a flavonoid compound that is found in scutellaria barbata. It has been reported to exhibit anticancer and anti-inflammation activities. However, the anticancer properties of scutellarin and its molecular targets have not been investigated in esophageal squamous cell carcinoma (ESCC). In the present study, we report that scutellarin is a potential AKT inhibitor that suppresses patient-derived xenograft ESCC tumor growth. To identify possible molecular targets of scutellarin, potential candidate proteins were screened by an in vitro kinase assay and Western blotting. We found that scutellarin directly binds to the AKT1/2 proteins and inhibits activities of AKT1/2 in vitro. The AKT protein is activated in ESCC tissues and knockdown of AKT significantly suppresses growth of ESCC cells. Scutellarin significantly inhibits anchorage-dependent and -independent cell growth and induces G2 phase cell cycle arrest in ESCC cells. The inhibition of cell growth by scutellarin is dependent on the expression of the AKT protein. Notably, scutellarin strongly suppresses patient-derived xenograft ESCC tumor growth in an in vivo mouse model. Taken together, our data suggest that scutellarin is a novel AKT inhibitor that may prevent progression of ESCC.

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