کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5841392 | 1560577 | 2016 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Miltirone induced mitochondrial dysfunction and ROS-dependent apoptosis in colon cancer cells Miltirone induced mitochondrial dysfunction and ROS-dependent apoptosis in colon cancer cells](/preview/png/5841392.png)
AimsTo study the characteristics of miltirone-induced anti-colon cancer effects.Materials and methodsCell viability was detected using MTT assay. LDH (lactate dehydrogenase) leakage was detected using CytoTox96® non-radioactive cytotoxicity kit. Apoptosis was detected by FCM (flow cytometry). Caspase activation was determined by chemiluminescence or western blotting. AIF (apoptosis-inducing factor) expression in the cell fraction was determined by western blotting. ROS (reactive oxygen species), MMP (mitochondrial membrane potential) and mitochondrial mass were determined by confocal microscope. Intracellular calcium was detected by both FCM and confocal microscope. To determine the roles of ROS and Ca2Â + in the pro-apoptotic activity of miltirone, colon cancer cells were pretreated with kinds of antioxidants, dicoumarol, calpeptin or BAPTA-AM in some cases.Key findingsMiltirone exhibited potent cytotoxicity on colon cancer cells with a better selectivity than that of dihydrotanshinone. The pro-apoptotic activity of miltirone was p53- and ROS-dependent. In detail, miltirone induced direct mitochondrial damage, including significant decrease of mitochondrial ROS, MMP, mass and increase of intracellular ROS and Ca2Â +. NQO1 (quinone oxidoreductase1) was supposed to be a defender for the cytotoxicity induced by miltirone in colon cancer cells. Furthermore, miltirone induced time- and concentration-dependent translocation of AIF and activation of caspases.SignificanceIn this study, ROS- and p53-dependent apoptosis induced by miltirone on colon cancer cells was firstly revealed. Strong positive feedback between mitochondrial dysfunction and accumulation of intracellular Ca2Â + was suggested to be the characteristic of the anti-colon cancer activity of miltirone.
Journal: Life Sciences - Volume 151, 15 April 2016, Pages 224-234