Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulationReportar como inadecuado




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BMC Complementary and Alternative Medicine

, 15:445

First Online: 22 December 2015Received: 14 June 2015Accepted: 14 December 2015

Abstract

BackgroundMelanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated.

MethodsMTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL-6 mice.

ResultsWe first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations 1, 3, and 10 μM. In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR-p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model.

ConclusionThe results of the present study indicate the potential utility of butein in the treatment of melanoma.

KeywordsMelanoma Butein Mammalian target of rapamycin Metastasis Vascular endothelial growth factor mTOR VEGF AbbreviationsPI3Kphosphatidylinositol 3-kinase

mTORmammalian target of rapamycin

p70S6Kp70S6 kinase

VEGFvascular endothelial growth factor

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Autor: Yu-Wei Lai - Shih-Wei Wang - Chien-Hsin Chang - Shih-Chia Liu - Yu-Jen Chen - Chih-Wen Chi - Li-Pin Chiu - Shiou-Sheng Che

Fuente: https://link.springer.com/







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