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Biochim Biophys Acta. 2013 Jun;1830(6):3835-45. doi: 10.1016/j.bbagen.2013.03.009. Epub 2013 Mar 15.

Oroxylin A sensitizes non-small cell lung cancer cells to anoikis via glucose-deprivation-like mechanisms: c-Src and hexokinase II.

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1
China Pharmaceutical University, Nanjing, People's Republic of China.

Abstract

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.

PMID:
23500080
DOI:
10.1016/j.bbagen.2013.03.009
[Indexed for MEDLINE]
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