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

BMC Complementary and Alternative Medicine

Research Article

Chih-Wen Chi¹  Yu-Jen Chen²  Ching-Hu Chung³  Shih-Wei Wang³  Shih-Chia Liu⁴  Allen W. Chiu⁵  Shiou-Sheng Chen⁵  Yu-Wei Lai⁵  Li-Pin Chiu⁵  Chien-Hsin Chang⁶ 

[1] Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan;Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan;Department of Medicine, Mackay Medical College, No. 46, Sec. 3, Jhong-Jheng Rd., Sanzhi Dist., Taipei, Taiwan;Department of Orthopaedics, Mackay Memorial Hospital, Taipei, Taiwan;Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan;Division of Urology, Taipei City Hospital Renai Branch, Taipei, Taiwan;Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan;

关键词: Melanoma;    Butein;    Mammalian target of rapamycin;    Metastasis;    Vascular endothelial growth factor;    mTOR;    VEGF;   

DOI  :  10.1186/s12906-015-0970-3

 received in 2015-06-14, accepted in 2015-12-14,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Lai et al. 2015