Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation.

Abstract

BACKGROUND:

Melanoma 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.

METHODS:

MTT 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.

RESULTS:

We 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.

CONCLUSION:

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

• Authors: Yu-Wei Lai, Shih-Wei Wang, Chien-Hsin Chang, Shih-Chia Liu, Yu-Jen Chen, Chih-Wen Chi, Li-Pin Chiu, Shiou-Sheng Chen, Allen W Chiu, Ching-Hu Chung
• Journal: BMC complementary and alternative medicine (BMC Complement Altern Med) Vol. 15 Pg. 445 (Dec 22 2015) ISSN: 1472-6882 [Electronic] England
• PMID: 26694191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Chalcones
• Vascular Endothelial Growth Factor A
• butein

Topics

• Animals
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chalcones (administration & dosage)
• Humans
• Male
• Melanoma, Experimental (drug therapy, metabolism, pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis
• Signal Transduction (drug effects)
• Skin Neoplasms (drug therapy, metabolism, pathology, physiopathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)