Scutellarin Suppresses Patient-Derived Xenograft Tumor Growth by Directly Targeting AKT in Esophageal Squamous Cell Carcinoma

Abstract

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 current 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 G 2 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.

PBK/TOPK: An Effective Drug Target with Diverse Therapeutic Potential

“…Moreover, SCU affects RPMI7951 cell growth by regulating the phosphorylation levels of ERK1/2 and histone H3 in a time- and dose-dependent manner [ 114 ]. Kim et al [ 121 ] found that SCU was a potential AKT inhibitor that inhibits patient-derived xenograft ESCC tumor growth. Given that AKT can act as a substrate of TOPK, it would be worthwhile studying whether SCU affects the expression of AKT by targeting TOPK.…”

Proteome and phosphoproteome reveal mechanisms of action of atorvastatin against esophageal squamous cell carcinoma

“…The basic processes of IHC were followed [36]. Briefly, paraffin-embedded tissues (5 μm) were prepared for IHC analysis.…”

Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers

“…Oridonin, Xanthohumol, and Scutellarin are natural compounds isolated from herbs. Their activities in targeting AKT activation in ESCC cells and ESCC-PDX have been reported [ 133 – 135 ]. These AKT inhibitors were effective in suppressing cell growth and inducing cell cycle arrest in ESCC cells as well as decreasing PDX tumor growth in vivo .…”

“…These AKT inhibitors were effective in suppressing cell growth and inducing cell cycle arrest in ESCC cells as well as decreasing PDX tumor growth in vivo . Importantly, the effects of these inhibitors were dependent on AKT protein level in ESCC cells [ 134 , 135 ].…”