In vitro and in vivo anti-tumor activity of CoQ 0 against melanoma cells: inhibition of metastasis and induction of cell-cycle arrest and apoptosis through modulation of Wnt/β-catenin signaling pathways
摘要：
Coenzyme Q0(CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a novel quinone derivative, has been shown to modulate cellular redox balance. However, effect of this compound on melanoma remains unclear. This study examined thein vitroorin vivoanti-tumor, apoptosis, and anti-metastasis activities of CoQ0(0-20 μM) through inhibition of Wnt/β-catenin signaling pathway. CoQ0exhibits a significant cytotoxic effect on melanoma cell lines (B16F10, B16F1, and A2058), while causing little toxicity toward normal (HaCaT) cells. The suppression of β-catenin was seen with CoQ0administration accompanied by a decrease in the expression of Wnt/β-catenin transcriptional target c-myc, cyclin D1, and survivin through GSK3β-independent pathway. We found that CoQ0treatment caused G1cell-cycle arrest by reducing the levels of cyclin E and CDK4. Furthermore, CoQ0treatment induced apoptosis through caspase-9/-3 activation, PARP degradation, Bcl-2/Bax dysregulation, and p53 expression. Notably, non- or sub-cytotoxic concentrations of CoQ0markedly inhibited migration and invasion, accompanied by the down-regulation of MMP-2 and -9, and up-regulation of TIMP-1 and -2 expressions in highly metastatic B16F10 cells. Furthermore, thein vivostudy results revealed that CoQ0treatment inhibited the tumor growth in B16F10 xenografted nude mice. Histological analysis and western blotting confirmed that CoQ0significantly decreased the xenografted tumor progression as demonstrated by induction of apoptosis, suppression of β-catenin, and inhibition of cell cycle-, apoptotic-, and metastatic-regulatory proteins. The data suggest that CoQ0unveils a novel mechanism by down-regulating Wnt/β-catenin pathways and could be used as a potential lead compound for melanoma chemotherapy.
展开
DOI：
10.18632/oncotarget.7983
被引量：
年份：
2016
通过文献互助平台发起求助，成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用！
