期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 33, 期 4, 页码 933-944出版社
KARGER
DOI: 10.1159/000358665
关键词
YLT205; Human colorectal cancer; Apoptosis; Mitochondrial pathway
Background: Colorectal cancer continues to be one of the most common causes of cancer death, and the poor survival rates and liver metastases at the time of diagnosis urgently need more effective strategy for colorectal cancer treatment. Methods: The activities of N-(5-bromopyridin-2-yl)-2-((6-(2-chloroacetamido) benzo[d] thiazol-2-yl) thio) acetamide (YLT205), which is a novel small molecule compound synthesized by us, were investigated using MTT assay, flow cytometry, western blotting and mice tumor xenograft models. Results: YLT205 induced apoptosis of human colorectal cell lines in a dose-dependent manner. The occurrence of apoptosis was associated with activation of caspases-9 and -3, down-regulation of Bcl-2 and up-regulation of Bax in HCT116 cells. Moreover, YLT205 disrupted mitochondrial membranes and induced the release of cytochrome c into cytosol. Impaired phosphorylation of p44/42 mitogen-activated protein kinase was also observed while the expression of phosphorylated protein kinase B (Akt) was not affected. Furthermore, in HCT116 and SW620 tumor-bearing nude mice models, YLT205 dose-dependently inhibited tumor growth without obvious adverse effects. Immunohistochemistry analyses revealed YLT205 also induced apoptosis and inhibited tumor cell proliferation in vivo. Conclusion: These studies suggested that YLT205 might be a potential drug candidate for human colorectal cancer therapy. Copyright (C) 2014 S. Karger AG, Basel
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据