A novel small-molecule YLT256 inhibits proliferation and induces apoptosis both in vitro and in vivo in solid tumors.
Pancreatic carcinoma is a still unsolved health problem all over the world with poor prognosis and high mortality rate. YLT256, a novel synthesized chemical small inhibitor, displays potent antineoplastic activities via inducing apoptosis both in vitro and in vivo. In this study, we found that YLT256 showed growth inhibition against a broad spectrum of human cancer cell lines and pancreatic cancer cell line BxPc-3 was the most sensitive with an IC50 of 0.42μM. We also found YLT256 could induce apoptosis of BxPc-3 cells in a dose-dependent manner. Western blot analysis revealed that the occurrence of its apoptosis was associated with activation of caspases-3 and -9, up-regulation of pro-apoptotic Bak, and down-regulation of anti-apoptotic Bcl-2. Moreover, YLT256-treated resulted in changes of mitochondrial membrane potential (Δψm), and generation of reactive oxygen species (ROS). Furthermore, our data also revealed that YLT256 suppressed the growth of established tumor-bearing xenograft models without obvious side effects. Immunohistochemical analyses and TUNEL assay revealed an increase in cleaved caspase-3-positive cells and TUNEL-positive cells, a decrease in Ki67-positive cells upon YLT256. Together, all the results of present study provided evidence demonstrating that YLT256 could be a promising potential drug candidate for pancreatic cancer therapy.
['Deng|Hongxia|H|', 'Zeng|Jun|J|', 'Zhu|Yongxia|Y|', 'Ye|Tinghong|T|', 'Xia|Yong|Y|', 'Shi|Yaojie|Y|', 'Wang|Ningyu|N|', 'Zhang|Lidan|L|', 'Song|Xuejiao|X|', 'Zuo|Weiqiong|W|', 'Gao|Tiantao|T|', 'Yu|Luoting|L|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D001549:Benzamides D045744:Cell Line, Tumor D049109:Cell Proliferation D048430:Cell Shape D002999:Clone Cells D005260:Female D006801:Humans D053078:Membrane Potential, Mitochondrial D008807:Mice, Inbred BALB C D008819:Mice, Nude D008954:Models, Biological D009363:Neoplasm Proteins D009369:Neoplasms D017382:Reactive Oxygen Species D054852:Small Molecule Libraries D013830:Thiadiazoles D023041:Xenograft Model Antitumor Assays
YLT256 Apoptosis Human pancreatic cancer Mitochondrial apoptosis pathway