Combined low dose ionizing radiation and green tea-derived epigallocatechin-3-gallate treatment induces human brain endothelial cells death.


:The microvasculature of brain tumors has been proposed as the primary target for ionizing radiation (IR)-induced apoptosis. However, the contribution of low dose IR-induced non-apoptotic cell death pathways has not been investigated. This study aimed to characterize the effect of IR on human brain microvascular endothelial cells (HBMEC) and to assess the combined effect of epigallocatechin-3-gallate (EGCg), a green tea-derived anti-angiogenic molecule. HBMEC were treated with EGCg, irradiated with a sublethal (< or =10 Gy) single dose. Cell survival was assessed 48 h later by nuclear cell counting and Trypan blue exclusion methods. Cell cycle distribution and DNA fragmentation were evaluated by flow cytometry (FC), cell death was assessed by fluorimetric caspase-3 activity, FC and immunoblotting for pro-apoptotic proteins. While low IR doses alone reduced cell survival by 30%, IR treatment was found more effective in EGCg pretreated-cells reaching 70% cell death. Analysis of cell cycle revealed that IR-induced cell accumulation in G2-phase. Expression of cyclin-dependent kinase inhibitors p21(CIP/Waf1) and p27(Kip) were increased by EGCg and IR. Although random DNA fragmentation increased by approximately 40% following combined EGCg/IR treatments, the synergistic reduction of cell survival was not related to increased pro-apoptotic caspase-3, caspase-9 and cytochrome C proteins. Cell necrosis increased 5-fold following combined EGCg/IR treatments while no changes in early or late apoptosis were observed. Our results suggest that the synergistic effects of combined EGCg/IR treatments may be related to necrosis, a non-apoptotic cell death pathway. Strategies sensitizing brain tumor-derived EC to IR may enhance the efficacy of radiotherapy and EGCg may represent such a potential agent.


J Neurooncol


McLaughlin N,Annabi B,Lachambre MP,Kim KS,Bahary JP,Moumdjian R,Béliveau R




Has Abstract


2006-11-01 00:00:00












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    authors: Koshiyama DB,Trevisan P,Graziadio C,Rosa RFM,Cunegatto B,Scholl J,Provenzi VO,de Sá AP,Soares FP,Velho MC,de A P Filho N,Oliveira CA,Zen PRG

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    authors: Pollack IF,Hamilton RL,Burger PC,Brat DJ,Rosenblum MK,Murdoch GH,Nikiforova MN,Holmes EJ,Zhou T,Cohen KJ,Jakacki RI,Children's Oncology Group.

    更新日期:2010-09-01 00:00:00

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    authors: Siffert J,Poussaint TY,Goumnerova LC,Scott RM,LaValley B,Tarbell NJ,Pomeroy SL

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    authors: Xu Z,Yen CP,Schlesinger D,Sheehan J

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    authors: Merlo EM,Maiolo A,Brocchieri A,Tua A,Grignani G

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    authors: Abouantoun TJ,Castellino RC,MacDonald TJ

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    authors: Cho N,Wang C,Raymond C,Kaprealian T,Ji M,Salamon N,Pope WB,Nghiemphu PL,Lai A,Cloughesy TF,Ellingson BM

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    authors: Landy H,Markoe A,Potter P,Lasalle G,Marini A,Savaraj N,Reis I,Heros D,Wangpaichitr M,Feun L

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Oikonomou E,Barreto DC,Soares B,De Marco L,Buchfelder M,Adams EF

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Pohar S,deMetz C,Poppema S,Hugh J

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Feun LG,Savaraj N,Landy H,Levin H,Lampidis T

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Bahary JP,Villemure JG,Choi S,Leblanc R,Olivier A,Bertrand G,Souhami L,Tampieri D,Hazel J

    更新日期:1996-02-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Barnes L,Kapadia SB

    更新日期:1994-01-01 00:00:00

  • Enhanced apoptosis in pilocytic astrocytoma: a comparative study of apoptosis and proliferation in astrocytic tumors.

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Nakamizo A,Inamura T,Ikezaki K,Yoshimoto K,Inoha S,Mizoguchi M,Amano T,Fukui M

    更新日期:2002-04-01 00:00:00

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    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Yoshida D,Nomura R,Teramoto A

    更新日期:2008-09-01 00:00:00

  • Nervous system lymphoid infiltration in Waldenström's macroglobulinemia. A case report.

    abstract::Neurological complications may occur in the course of Waldenström's macroglobulinemia (Wm). These complications affect both the central and peripheral nervous system. Pathogenesis is debated and several mechanisms have been suggested. Direct malignant lymphoid infiltration (MLI) is very rare and has only been reported...

    journal_title:Journal of neuro-oncology

    pub_type: 杂志文章


    authors: Massengo S,Riffaud L,Morandi X,Bernard M,Verin M

    更新日期:2003-05-01 00:00:00