文献类型：会议

作　　者：周千翔 唐生安 矢守隆夫 旦慎吾 孔德新

作者单位：日本癌研究会分子药理部 天津医科大学药学院生物制药教研室、基础医学研究中心分子靶向药物研究室

会议文献：2014年中国药学大会暨第十四届中国药师周论文集

会议名称：2014年中国药学大会暨第十四届中国药师周

会议日期：20141024

会议地点：石家庄

主办单位：中国药学会

出版日期：20141024

语　　种：中文

摘　　要：Stel B (Stellettin B) was isolated from marine sponge Jaspis stellifera.In vitro antitumor activities were investigated on 39 human cancer cell lines (JFCR39).Stel B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295,with a GI50 of 0.03 μM.In contrast,Stel B showed very weak inhibitory activity on normal cell lines including HMEC,RPTEC,NHBE and PrEC,with GI50s higher than 10 μM,suggesting its low toxicity.We then focused on the antitumor activity of this compound on SF295 cells.Flow cytometric analysis via PI staining as well as Annexin V/PI double staining indicated that Stel B induced apoptosis in SF295 cells in a concentration-dependent manner.Further study indicated that Stel B increased the production of ROS,the activity of caspase 3/7,as well as the cleavage of PARP,each of which is known to be involved in apoptosis.To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction,effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined.Stel B inhibited the phosphorylation of Akt potently,with no activity on p-ERK and p-p38,suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect.However,homogenous time-resolved fluorescence (HTRF) assay indicated that Stel B did not inhibit PI3K activity,suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.

关 键 词：Stellettin  B  marine  sponge,antitumor  in  VITRO JFCR39  PI3K/AKT pathway  

分 类 号：ZZ]