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http://purl.uniprot.org/citations/23500080http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Cellular metabolism, particularly glycolysis, is altered during the metastatic process and is highly associated with tumor progression and apoptosis resistance. Oroxylin A, a natural plant flavonoid, exhibits chemopreventive and therapeutic anti-inflammatory and anticancer potential. However, the anticancer effects of oroxylin A on non-small cell lung carcinoma (NSCLC) remain poorly understood.

Methods

In vitro studies were performed using 2D and 3D conditions. The effects on anoikis-sensitization and glycolysis-inhibition of oroxylin A in human non-small cell lung cancer A549 cells were examined. In vivo murine lung metastasis experiments were utilized to assess the anti-metastatic capacity of oroxylin A.

Results

ROS-mediated activation of c-Src following detachment caused anoikis resistance in A549 cells. Oroxylin A sensitized A549 cells to anoikis by inactivating the c-Src/AKT/HK II pathway in addition to inducing the dissociation of HK II from mitochondria. Prior to sensitizing A549 cells to anoikis, oroxylin A decreased the ATP level and inhibited glycolysis. Furthermore, oroxylin A inhibited lung metastasis of A549 cells in vivo in nude mice.

Conclusions

Oroxylin A sensitized anoikis, which underlies distinct glucose-deprivation-like mechanisms that involved c-Src and HK II.

General significance

The findings in this study indicated that oroxylin A could potentially be utilized in the development of improved metastatic cancer treatments."xsd:string
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http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/author"Li Z."xsd:string
http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/author"Zhou Y."xsd:string
http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/author"Wei L."xsd:string
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http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/author"Lu N."xsd:string
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http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/name"Biochim Biophys Acta"xsd:string
http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/pages"3835-3845"xsd:string
http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/title"Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II."xsd:string
http://purl.uniprot.org/citations/23500080http://purl.uniprot.org/core/volume"1830"xsd:string
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