A Novel Small-Molecule YLT205 Induces Apoptosis in Human Colorectal Cells via Mitochondrial Apoptosis Pathway In Vitro and Inhibits Tumor Growth In Vivo
| Autor: | Luoting Yu, Yuanping Han, Ningyu Wang, Yong Luo, Xuan-Hong Shi, Tinghong Ye, Yongxia Zhu, Li Liu, Xuejiao Song, Yong Xia, Jun Zeng |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Physiology
Colorectal cancer Cell Survival Transplantation Heterologous Down-Regulation Mice Nude Apoptosis Mouse model of colorectal and intestinal cancer Biology lcsh:Physiology Amino Acid Chloromethyl Ketones lcsh:Biochemistry Mice In vivo Cell Line Tumor Acetamides medicine Animals Humans MTT assay lcsh:QD415-436 Benzothiazoles Phosphorylation Protein kinase A Protein kinase B bcl-2-Associated X Protein Flavonoids Membrane Potential Mitochondrial lcsh:QP1-981 Cytochrome c Cytochromes c Mitochondrial pathway medicine.disease HCT116 Cells Molecular biology Mitochondria YLT205 biology.protein Human colorectal cancer Colorectal Neoplasms |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 33, Iss 4, Pp 933-944 (2014) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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