全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

(R)-Roscovitine诱导Hela细胞凋亡的分子机制

DOI: 10.11830/ISSN.1000-5013.2013.04.0422

Keywords: (R)-roscovitine, 细胞周期蛋白依赖性激酶, 细胞凋亡, 凋亡诱导因子, 半胱天冬酶

Full-Text   Cite this paper   Add to My Lib

Abstract:

以Hela细胞为模型, 探讨细胞周期蛋白依赖性激酶抑制剂(R)-roscovitine对Hela细胞凋亡诱导的可能途径, 进一步了解其诱导肿瘤细胞凋亡的分子机制.结果显示:(R)-roscovitine明显抑制Hela细胞的增殖,在17.5~140.0 μmol?L-1浓度作用12,24,48 h后,Hela细胞的增殖抑制率分别为8.48%~33.76%,25.19%~86.41%和47.90%~88.08%;典型凋亡的DNA ladder被诱导,且凋亡率随药物浓度的增加而升高;经半胱天冬酶-3(caspase-3)特异性抑制剂Ac-DEVD-CHO或半胱天冬酶泛抑制剂Z-VAD-FMK处理后,(R)-roscovitine对Hela细胞凋亡的诱导被抑制约20%,说明半胱天冬酶依赖的途径参与了(R)-roscovitine对Hela细胞凋亡的诱导;(R)-roscovitine诱导凋亡诱导因子(AIF)从线粒体释放细胞核中,且Ac-DEVD-CHO和Z-VAD-FMK没有抑制AIF的释放,这意味着(R)-roscovitine能够诱导Hela细胞凋亡,其机制是通过caspase与非caspase依赖两种途径.

References

[1]  DICKSON M A,SCHWARTZ G K.Development of cell-cycle inhibitors for cancer therapy[J].Curr Oncol,2009,16(2):36-43.
[2]  ALDOSS I T,TASHI T,GANTI A K.Seliciclib in malignancies[J].Expert Opin Inv Drug,2009,18(12):1957-1965.
[3]  MEIJER L.Chemical inhibitors of cyclin-dependent kinesis[J].Trends Cell Biol,1996,6(10):393-397.
[4]  MGBONYEBI O P,RUSSO J,RUSSO I H.Roscovitine induces cell death and morphologicalchanges indicative of apoptosis in MDA-MB-231 breast cancer cells[J].Cancer Res,1999,59(8):1903-1910.
[5]  ALVI A J,AUSTEN B,WESTON V J,et al.A novel CDK inhibitor,CYC202(R-roscovitine), overcomes the defect in p53-dependent apoptosis in B-CLL by down-regulation of genes involved in transcription regulation and survival[J].Blood,2005,105(11):4484-4491.
[6]  APPLEYARD M V,O’NEILL M A,MURRAY K E,et al.Seliciclib(CYC202, R-roscovitine)enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model[J].Int J Cancer,2009,124(2):465-472.
[7]  LJUNGMAN M,PAULSEN M T.The cyclin-dependent kinase inhibitor roscovitine inhibits RNA synthesis and triggers nuclear accumulation of p53 that is unmodified at Ser15 and Lys382[J].Mol Pharmacol,2001,60(4):785-789.
[8]  高建新,周玉琴,张茹华,等.Caspase-3在roscovitine诱发PC12细胞凋亡中发挥重要作用[J].生理学报,2005,57(6):755-760.
[9]  于翠娟,王成济,杨安钢.AIF及AIF依赖的凋亡[J].医学分子生物学杂志,2003,25(6):351-353.
[10]  赵文丽.细胞凋亡及其检测技术的进展[J].山西职工医学院学报,2004,14(2):68-69.
[11]  CANDé C,CECCONI F,DESSEN P,et al.Apoptosis-inducing factor(AIF): Key to the conserved caspase-independent pathways of cell death?[J].J Cell Sci,2002,115(24):4727-4734.
[12]  SUSIN S A,LORENZO H K,ZAMZAMI N,et al.Molecular characterization of mitoch-ondrial apoptosis-inducing factor[J].Nature,1999,397(6718):441-446.
[13]  陈默,潘敏慧,周恩昆,等.凋亡诱导因子的研究进展[J].细胞生物学杂志,2007,29(6):791-794.
[14]  HUANG H,REGAN KM,LOU Z,et al.CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage[J].Science,2006,314(5797):294-297.
[15]  RAYNAUD F I,WHITTAKER S R,FISCHER P M,et al.In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine,bohemine and CYC202[J].Clin Cancer Res,2005,11(13):4875-4887.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133