P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent,but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells
P53-mediated cell cycle arrest and apoptosis through a caspase-3-independent,but caspase-9-dependent pathway in oridonin-treated MCF-7 human breast cancer cells作者机构:Department of Clinical and Biomedical SciencesShowa Pharmaceutical University Tokyo 194-8543Japan Department of ImmunologyYokohama City University School of MedicineYokohama 235-0004Japan China-Japan Research Institute of Medical Pharmaceutical SciencesShenyang Pharmaceutical UniversityShenyang 110016China
出 版 物:《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期:2007年第28卷第7期
页 面:1057-1066页
核心收录:
学科分类:1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题:oridonin MCF-7 cells cell cycle arrest apoptosis p53 caspase-9 caspase-3 calpain mitochondrial pathway
摘 要:Aim:To study the caspase-3-independent mechanisms in oridonin-induced MCF-7human breast cancer cell apoptosis in ***:The viability of oridonin-treated MCF-7 cells was measured by MTT (thiazole blue) *** cellswith condensed nuclei were visualized by phase contrast ***-mal DNA fragmentation was assayed by agarose gel *** apoptoticratio was determined by lactate dehydrogenase *** cycle alternation andmitochondrial membrane potential were measured by flow cytometric ***,Bcl-2,caspase-3,caspase-9,heat shock protein (Hsp)90,p53,p-p53,p21,Poly(ADP-ribose) polymerase (PARP),and the inhibitor of caspase-activated DNase(ICAD) protein expressions were detected by Western blot ***:Oridonin inhibited cell growth in a time-and dose-dependent *** cyclewas altered through the upregulation of p53 and p21 protein ***-caspase inhibitor Z-VAD-fmk and calpain inhibitor Ⅱ both decreased cell *** DNA fragmentation and the downregulation of ΔΨmitweredetected in oridonin-induced MCF-7 cell apoptosis,which was involved in apostmitochondrial caspase-9-dependent *** Bcl-2 and Hsp90expression levels and increased Bax and p21 expression levels were positivelycorrelated with elevated levels of phosphorylated p53 ***,PARP was partially cleaved by calpain rather than by ***:DNAdamage provoked alternations in the mitochondrial and caspase-9 pathways aswell as p53-mediated cell cycle arrest,but was not related to caspase-3 activity inoridonin-induced MCF-7 cells.