کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5558247 | 1561128 | 2017 | 12 صفحه PDF | دانلود رایگان |
- Quinacrine induces U937 cell apoptosis via upregulation of BAX.
- Quinacrine induces FOXP3 expression via p38 MAPK activation and ERK inactivation.
- FOXP3-mediated miR-183 expression reduces β-TrCP mRNA stability.
- Suppression of β-TrCP-mediated SP1 degradation increases BAX expression.
- Quinacrine elicits FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation.
Quinacrine, which is clinically used as an antimalarial drug, has anti-cancer activity. However, mechanism underlying its cytotoxic effect remains to be completely elucidated. In the present study, we investigated the cytotoxic effect of quinacrine on human leukemia U937 cells. Quinacrine-induced apoptosis of U937 cells was accompanied with ROS generation, mitochondrial depolarization, and BAX upregulation. Quinacrine-treated U937 cells showed ROS-mediated p38 MAPK activation and ERK inactivation, which in turn upregulated FOXP3 transcription. FOXP3-mediated miR-183 expression decreased β-TrCP mRNA stability and suppressed β-TrCP-mediated SP1 degradation, thus increasing SP1 expression in U937 cells. Upregulated SP1 expression further increased BAX expression. BAX knock-down attenuated quinacrine-induced mitochondrial depolarization and increased the viability of quinacrine-treated cells. Together, our data indicate that quinacrine-induced apoptosis of U937 cells is mediated by mitochondrial alterations triggered by FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation.
Journal: Toxicology and Applied Pharmacology - Volume 334, 1 November 2017, Pages 35-46