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Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis.

Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Research Abstract Details 

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  • Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Abstract Text:

    yide meiYide Mei,chongwei xieChongwei Xie,wei xieWei Xie,xu tianXu Tian,mei liMei Li,mian wuMian Wu,yide meiYide Mei,chongwei xieChongwei Xie,wei xieWei Xie,xu tianXu Tian,mei liMei Li,mian wuMian Wu,

    Although camptothecin (CPT) has been reported to induce apoptosis in various cancer cells, the molecular details of this regulation remain largely unknown. In this study, we demonstrate that BH3-only protein Noxa is upregulated during CPT-induced apoptosis, which is independent of p53. In addition, we show that phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is responsible for Noxa's induction. Luciferase assay and cAMP response element binding protein (CREB) knockdown experiments further demonstrate that CREB is involved in the transcriptional upregulation of Noxa. Moreover, blocking Noxa expression using specific small interfering ribonucleic acid (siRNA) significantly reduces the apoptosis in response to CPT, indicating that Noxa is an essential mediator for CPT-induced apoptosis. Interestingly, antiapoptotic Mcl-1 was also upregulated through PI3K/Akt signaling pathway upon CPT treatment. Using immunoprecipitation assay, Noxa was found to interact with Mcl-1 in the presence or absence of CPT. Knockdown of Mcl-1 expression by short hairpin ribonucleic acid (shRNA) was shown to potentiate CPT-induced apoptosis. Consistently, ectopic overexpression of Mcl-1 rescued cells from apoptosis induced by CPT. Cells coexpressing Noxa and Mcl-1 at different ratio correlates well with the extent of apoptosis, suggesting that the balance between Noxa and Mcl-1 may determine the susceptibility of HeLa cells to CPT-induced apoptosis.

    Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Publishing Authors By Initials

    y meiY Mei,c xieC Xie,w xieW Xie,x tianX Tian,m liM Li,m wuM Wu,y meiY Mei,c xieC Xie,w xieW Xie,x tianX Tian,m liM Li,m wuM Wu,

    For similar abstracts research abstracts see: abstracts research

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    Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Neoplasia (New York, N.Y.)

    VOLUME: 9

    Page Numbers: 871-81

    Journal Abbreviation: Neoplasia

    ISSN: 1476-5586

    DAY: 31

    MONTH: Oct

    YEAR: 2007

    Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Information

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    LANGUAGE: eng

    NlmUniqueID: 100886622

    Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis. Keywords Mesh Terms:

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    Grant and Affiliation Information for Noxa/Mcl-1 balance regulates susceptibility of cells to camptothecin-induced apoptosis.

    AFFILIATION: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.

    Country: Canada

    Canada Research PublicationCanada Research Publication

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    MEDLINETA: Neoplasia

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