کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8294864 | 1536755 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Osteosarcoma is a common primary malignant bone tumor, the cure rate of which has stagnated over the past 25-30 years. Autophagy modulation has been considered a potential therapeutic strategy for osteosarcoma, and previous study indicated that arsenic trioxide (ATO) exhibits significant anti-carcinogenic activity. However, the ability of ATO to induce autophagy and its role in osteosarcoma cell death remains unclear. In the present study, we showed that ATO increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blocking autophagy decreased ATO -induced cell death, indicating that ATO triggered autophagic cell death in MG-63â¯cells. Mechanistically, ATO induced TFEB(Ser142) dephosphorylation, activated TFEB nuclear translocation and increased TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63â¯cells. Importantly, ATO triggered the generation of ROS in MG-63â¯cells. Furthermore, NAC, an ROS scavenger, abrogated the effects of ATO on TFEB-dependent autophagic cell death. Taken together, these data demonstrate that ATO induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS-TFEB pathway. The present study provides a new anti-tumor mechanism of ATO treatment in osteosarcoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 496, Issue 1, 29 January 2018, Pages 167-175
Journal: Biochemical and Biophysical Research Communications - Volume 496, Issue 1, 29 January 2018, Pages 167-175
نویسندگان
Bowen Wu, Miduo Tan, Weiliang Cai, Biao Wang, Peiheng He, Xiping Zhang,