کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10156671 1666418 2018 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The anti-malarial atovaquone selectively increases chemosensitivity in retinoblastoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The anti-malarial atovaquone selectively increases chemosensitivity in retinoblastoma via mitochondrial dysfunction-dependent oxidative damage and Akt/AMPK/mTOR inhibition
چکیده انگلیسی
Mitochondria has been identified as a promising target in several cancers. However, little is known on the effects of targeting mitochondria in retinoblastoma. In this work, we show that anti-malarial atovaquone, at clinically achievable concentration, demonstrates inhibitory effects to retinoblastoma cells, to a more extent than in normal retinal cells. Atovaquone also significantly increases chemosensitivity in retinoblastoma. Importantly, we show that retinoblastoma cells have higher level of mitochondrial respiration, membrane potential, mass and ATP compared to normal retinal cells. Although atovaquone significantly inhibits mitochondrial respiration and decrease ATP level in both malignant and normal retinal cells in a similar manner, atovaquone induces much more oxidative stress and damage in retinoblastoma than normal retinal cells. These suggest that normal retinal cells are more tolerable to mitochondrial dysfunctions than retinoblastoma cells. We further demonstrate that atovaquone targets Akt/AMPK/mTOR signaling via inducing mitochondrial dysfunction. Our pre-clinical work demonstrates the translational potential of atovaquone as an addition to the treatment armamentarium for retinoblastoma. Our work also demonstrates the differences of mitochondrial biogenesis and function in malignant versus normal retinal cells which are important for the targeted therapy in retinoblastoma.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 504, Issue 2, 2 October 2018, Pages 374-379
نویسندگان
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