کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3947103 1254406 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی زنان، زایمان و بهداشت زنان
پیش نمایش صفحه اول مقاله
Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells
چکیده انگلیسی

ObjectiveEpithelial ovarian cancer (EOC) cells are known to be resistant to apoptosis through a mechanism that may involve alteration in their redox balance. NADPH oxidase is a major source of intracellular superoxide, which is converted to the less toxic product by superoxide dismutase (SOD). Superoxide contributes to hypoxia inducible factor (HIF)-1α stabilization. We sought to determine the effects of inhibiting the generation of intracellular reactive oxygen species (ROS) on apoptosis of EOC cells.MethodsDiphenyleneiodonium (DPI), an irreversible ROS inhibitor, was used to inhibit the generation of ROS in EOC cell lines, SKOV-3 and MDAH-2774, followed by assessment of apoptosis, NADPH oxidase, SOD3 and HIF-1α expression. A combination of immunohistochemistry, immunoprecipitation/western blot, and real-time RT-PCR were utilized to evaluate the expression of these enzymes in EOC cells as well as normal ovarian tissue and ovarian cancer tissue specimens.ResultsDPI treatment significantly induced apoptosis in both EOC cell lines as evident by increased caspase-3 activity and TUNEL assay. Additionally, both EOC cell lines were found to express NADPH oxidase, HIF-1α, and SOD3, which were highly sensitive to DPI treatment. DPI treatment resulted in reduced NADPH oxidase, SOD3 and HIF-1α levels. Furthermore, ovarian cancer tissues were found to manifest higher NADPH oxidase levels as compared to normal ovarian tissues.ConclusionsThese data suggest that lowering oxidative stress, possibly through the inhibition of NADPH oxidase, induces apoptosis in ovarian cancer cells and may serve as a potential target for cancer therapy.

Research highlights
► Epithelial ovarian cancer (EOC) cells are resistant to apoptosis.
► Diphenyleneiodonium (DPI) inhibits generation of ROS, such as superoxide.
► Modulating oxidative stress induces apoptosis and serves as a potential therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gynecologic Oncology - Volume 122, Issue 2, August 2011, Pages 418–423
نویسندگان
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