کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8544671 | 1561552 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Vosaroxin induces mitochondrial dysfunction and apoptosis in cervical cancer HeLa cells: Involvement of AMPK/Sirt3/HIF-1 pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Vosaroxin induces mitochondrial dysfunction and apoptosis in cervical cancer HeLa cells: Involvement of AMPK/Sirt3/HIF-1 pathway Vosaroxin induces mitochondrial dysfunction and apoptosis in cervical cancer HeLa cells: Involvement of AMPK/Sirt3/HIF-1 pathway](/preview/png/8544671.png)
چکیده انگلیسی
Vosaroxin is a quinolone-derivative anticancer agent with inhibitory activity on type II DNA topoisomerases (TOP2). The aim of the present study was to investigate its cytotoxic effect and potential molecular mechanisms in human cervical cancer HeLa cells. Vosaroxin decreased cell viability and increased lactate dehydrogenase (LDH) release in a dose- and time-dependent manner in HeLa cells, but not in normal cervical epithelial cells. Vosaroxin also induced apoptosis and increased caspase-3 activity in HeLa cells. These effects were accompanied by increased mitochondrial reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial swelling and reduced ATP production. Western blot analysis showed that vosaroxin significantly reduced hypoxia-inducible factor 1α (HIF-1α) protein levels. However, it had no effect on HIF-1α protein degradation and HIF-1α mRNA levels. The results showed that vosaroxin inhibited the synthesis of HIF-1α protein and interfered with the dimerization of HIF-1α and aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, vosaroxin stimulated mitochondrial enzyme activities and superoxide dismutase 2 (SOD2) deacetylation via activating (Sir2 like protein 3) Sirt3. More importantly, vosaroxin-induced inhibition on HIF-1α and its cytotoxic effects, as measured by cell viability, LDH release and apoptosis, were partially prevented by Sirt3 knockdown or the AMP-activated protein kinase (AMPK) inhibitor compound C. Overall, vosaroxin is demonstrated to be a chemotherapeutic agent targeting the Sirt3/HIF-1 pathway and could be beneficial for inducing cytotoxicity in human cervical cancer cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 290, 25 June 2018, Pages 57-63
Journal: Chemico-Biological Interactions - Volume 290, 25 June 2018, Pages 57-63
نویسندگان
Xian-Li Zhao, Chun-Zhi Yu,