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 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.
Highlights
Esophageal cancer is the sixth leading cause of cancerrelated death in the world [1]
Results showed that phosphorylated Akt murine thymoma viral oncogene homolog (AKT) was highly expressed in the EG30 esophageal squamous cell carcinoma (ESCC) tissue (Supplementary Fig. S3; Supplementary Table S1), and the EG30 tissue was used for the patientderived xenograft (PDX) study
A, The effect of scutellarin on esophageal cancer cell growth was assessed in cells stably expressing shAKT1 and shAKT2 or cells stably expressing shControl
Summary
Esophageal cancer is the sixth leading cause of cancerrelated death in the world [1]. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer that accounts for more than 50% of global ESCC cases most in China [2]. Despite clinical advances in therapeutics, such as endoscopic resection, radiotherapy, and chemotherapy, the 5-year survival rate of patients with esophageal cancer is still less than. Note: Supplementary data for this article are available at Cancer Prevention Research Online (http://cancerprevres.aacrjournals.org/). High-throughput sequencing technologies have been investigated to identify the genomic alterations in ESCC [4, 5]. RTK inhibitors have been examined to treat patients with ESCC, but these inhibitors have shown limited responses [6]. Finding novel targets against ESCC has been a priority [7]
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