کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10584239 | 981327 | 2014 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Involvement of apoptosis and autophagy in the death of RPMI 8226 multiple myeloma cells by two enantiomeric sigma receptor ligands
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کلمات کلیدی
3-MADCFDABmaxPI3KMMPPBSPARPDAPILC3BDTGLPOIC50tBH2′,7′-dichlorofluorescein diacetate - 2 '، 7'-dichlorofluorescein diacetate3-methyladenine - 3-متیل آدنین4,6-diamino-2-phenylindole - 4،6-دیامینو-2-فنیلینولDMSO - DMSOMTT - MTTROS - ROSz-VAD-fmk - Z-VAD-FMKAutophagy - اتوفاژیstandard deviation - انحراف معیارApoptosis - خزان یاختهایstandard error of mean - خطای استاندارد میانگینDimethylsulfoxide - دیمتیل سولفواکسیدmicrotubule-associated protein light chain 3 - زنجیره سبک پروتئینی مرتبط با میکروتوبول 3Cancer - سرطانPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازSEM - مدل معادلات ساختاری / میکروسکوپ الکترونی روبشیApoptosis inhibitor - مهار کننده آپوپتوزMitochondrial membrane potential - پتانسیل غشای میتوکندریLipid peroxidation - پراکسیداسیون لیپیدPropidium iodide - پروتئین یدیدPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Over-expression of Ï receptors by many tumor cell lines makes ligands for these receptors attractive as potential chemotherapeutic drugs. Enantiomeric piperazines (S)-4 and (R)-4 were prepared as potential Ï-receptor ligands in a chiral pool synthesis starting from (S)- and (R)-aspartate. Both compounds showed high affinities for the Ï1 and Ï2 receptors. In the human multiple myeloma cell line RPMI 8226, a line expressing high levels of Ï receptors, both compounds inhibited cell proliferation with IC50 values in the low μM range. No chiral differentiation between either the Ï receptor binding affinity or the cytotoxicity of the two enantiomers was observed. Both compounds induced apoptosis, which was evidenced by nuclear condensation, binding of annexin-V to phosphatidylserine in the outer leaf of the cell membrane, cleavage products of poly(ADP-ribose) polymerase-1 (PARP-1) and caspase-8 as well as the expression of bcl2 family members bax, bad and bid. However, apoptosis appeared to be caspase independent. Increased levels of the phosphorylated form of the microtubule associated protein light chain 3-II (LC3-II), an autophagosome marker, gave evidence that both compounds induced autophagy. However, further data (e.g., treatment with wortmannin) indicate that autophagy is incomplete and not cytoprotective. Lipid peroxidation (LPO) was observed in RPMI 8226 cells treated with the two compounds, and the lipid antioxidant α-tocopherol attenuated LPO. Interestingly, α-tocopherol reduced significantly both apoptosis and autophagy induced by the compounds. These results provide evidence that, by initiating LPO and changes in mitochondrial membrane potential, both compounds induce apoptosis and autophagy in RPMI 8226 cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 1, 1 January 2014, Pages 221-233
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 1, 1 January 2014, Pages 221-233
نویسندگان
Katharina Korpis, Frauke Weber, Stefanie Brune, Bernhard Wünsch, Patrick J. Bednarski,