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Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2 / Bax and activating caspase-3 / ICAD pathway
引用本文:Zhang CL,Wu LJ,Tashiro S,Onodera S,Ikejima T. Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2 / Bax and activating caspase-3 / ICAD pathway[J]. Acta pharmacologica Sinica, 2004, 25(5): 691-698
作者姓名:Zhang CL  Wu LJ  Tashiro S  Onodera S  Ikejima T
作者单位:Department of Clinical and Biomedical Sciences,Showa College of Pharmaceutical Sciences,Tokyo 194-8543,Japan,Department of Clinical and Biomedical Sciences,Showa College of Pharmaceutical Sciences,Tokyo 194-8543,Japan,China-Japan Research Institute of Medical and Pharmaceutical Sciences,Shenyang Pharmaceutical University,Shenyang 110016,China,prof
摘    要:INTRODUCTIONHerbal medicine, Donglingcao (rabdosiarubescens), has been traditionally used in China for thetreatment of various diseases such as leukemia.Oridonin (Fig 1) is a diterpenoid compound isolated fromRabdosia rubescens (hemsl). It has various pharmaco-logical and physiological effects such as anti-inflammation, anti-bacteria, anti-tumor[1-3] and has beenused for the treatment of human cancers, especiallyFig 1. Chemical structure of oridonin.esophageal carcinoma[4]. This comp…

关 键 词:半胱氨酸蛋白酶  细胞凋亡  HeLa细胞  Bcl-2基因  Bax基因  免疫印迹法  冬凌草甲素

Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway
Zhang Chun-Ling,Wu Li-Jun,Tashiro Shin-Ichi,Onodera Satoshi,Ikejima Takashi. Oridonin induces apoptosis of HeLa cells via altering expression of Bcl-2/Bax and activating caspase-3/ICAD pathway[J]. Acta pharmacologica Sinica, 2004, 25(5): 691-698
Authors:Zhang Chun-Ling  Wu Li-Jun  Tashiro Shin-Ichi  Onodera Satoshi  Ikejima Takashi
Affiliation:[1]1China-JapanResearchInstituteofMedicalandPharmaceuticalSciences,ShenyangPharmaceuticalUniversity,Shenyang110016,China [2]DepartmentofPhytochemistry,ShenyangPharmaceuticalUniversity,Shenyang110016,China [3]DepartmentofClinicalandBiomedicalSciences,ShowaCollegeofPharmaceuticalSciences,Tokyo194-8543,Japan [4]CorrespondencetoProfTakashiIKEJIMA,ShowaCollegeofPharmaceuticalSciences,Tokyo194-8543,Japan
Abstract:To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability of oridonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis.Caspase activity was assayed using fluorometric protease assay. ICAD, Bcl-2, and Bax proteins expression were detected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA and increased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase (ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activation and down-regulation of ICAD expression were effectively inlfibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). However, pretreatment with an inhibitor ofpoly (ADP-ribose) polymerase (PARP), 3, 4-dihydro-5-[4-(1-piperidinyl)butoxy]-l(2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. In addition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducer Bax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION:Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation of caspase-3/ICAD pathway.
Keywords:oridonin  HeLa cells  apoptosis  caspase 3  caspases  bcl-2 genes  bax genes  Western blotting  
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