کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2754444 1149784 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Antiproliferative and Proapoptotic Effects of Topotecan in Combination With Thymoquinone on Acute Myelogenous Leukemia
ترجمه فارسی عنوان
اثرات ضدپروپلیفراتیو و پرواپوپتوزی تپتاکان در ترکیب با تیوگوینون بر لوسمی مگنی حاد
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
چکیده انگلیسی

Background: Topotecan has shown promising antineoplastic activity in solid tumors and acute leukemia. Because of the primary dose-limiting toxicity of topotecan, it is necessary to identify other agents that can work synergistically with topotecan, potentially increasing its efficacy while limiting its toxicity. Many studies showed synergism in combination of topotecan with gemcitabine and bortezomib. Other studies report the increase in growth inhibition of gemcitabine or oxaliplatin when cells were preexposed to naturally occurring drugs such as thymoquinone. The aim of this project was to study the mode of action of topotecan along with thymoquinone, on survival and apoptosis pathways in acute myelogenous leukemia (AML) cell lines, and to investigate the potential synergistic effect of thymoquinone on topotecan.Materials and MethodsU937 cells were incubated with different topotecan and thymoquinone concentrations for 24 and 48 hours, separately and in combination. Cell proliferation was determined using WST-1 (Roche) reagent. The effect of the compounds on protein expression of Bax, Bcl2, p53, caspase-9, -8, and -3 was determined using Western blot analysis. Cell cycle analysis was performed in addition to annexin/propidium iodide staining.ResultsThymoquinone and topotecan exhibited antiproliferative effects on U937 cells when applied separately. In combination, the reduction in proliferation was extremely significant with a major increase in the expression levels of Bax/Bcl2, p53, and caspase-3 and -9. Preexposure with thymoquinone resulted in an increase in cell growth inhibition compared with topotecan treatment.ConclusionThymoquinone, when combined with topotecan in noncytotoxic doses, produced synergistic antiproliferative and proapoptotic effects in AML cells. Preexposure to thymoquinone seems to be more effective than simultaneous application with topotecan.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Lymphoma Myeloma and Leukemia - Volume 14, Supplement, September 2014, Pages S46–S55
نویسندگان
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