Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.
Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.
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DOI：
10.1054/bjoc.2001.2142
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发表时间：
2001-11-16
影响因子：
8.8
通讯作者：
Marko D
中科院分区：
文献类型：
--
作者：
Barthelmes HU;Niederberger E;Roth T;Schulte K;Tang WC;Boege F;Fiebig HH;Eisenbrand G;Marko D
石蒜甜菜碱是石蒜科植物的一种微量成分。在克隆形成试验中，对21例人肿瘤异种移植物的细胞生长抑制进行了研究（平均IC 50 = 0.8 μM）。 人白血病细胞系的生长也受到强效抑制（平均IC 50 = 1.3 μM）。 无胸腺裸鼠，携带s.c.用番茄甜菜碱腹膜内处理植入的人胃肿瘤异种移植物GXF 251 4周，导致显著的肿瘤生长延迟。发现石蒜甜菜碱作为一种特异性拓扑异构酶IIβ毒物。在小牛胸腺DNA存在下，从SDS-凝胶中选择性地去除纯的重组人拓扑异构酶IIβ蛋白，而没有观察到拓扑异构酶IIα蛋白的去除。在A431细胞中，诱导拓扑异构酶IIβ的免疫带耗竭，表明活细胞中共价催化DNA中间体的稳定化。可以合理地假设该机制将导致或至少显著促进抗肿瘤活性。2001癌症研究运动 http://www.bjcancer.com
The phenanthridine alkaloid lycobetaine is a minor constituent of Amaryllidaceae. Inhibition of cell growth was studied in the clonogenic assay on 21 human tumour xenografts (mean IC 50 = 0.8 μM). The growth of human leukaemia cell lines was also potently inhibited (mean IC 50 = 1.3 μM). Athymic nude mice, carrying s.c. implanted human gastric tumour xenograft GXF251, were treated i.p. with lycobetaine for 4 weeks, resulting in a marked tumour growth delay. Lycobetaine was found to act as a specific topoisomerase IIβ poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase IIβ protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase IIα protein was observed. In A431 cells immunoband-depletion of topoisomerase IIβ was induced, suggesting stabilization of the covalent catalytic DNA-intermediate in living cells. It is reasonable to assume that this mechanism will cause or at least contribute significantly to the antitumour activity. © 2001 Cancer Research Campaign http://www.bjcancer.com
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影响因子：
8.8
作者：
Marko D;Schätzle S;Friedel A;Genzlinger A;Zankl H;Meijer L;Eisenbrand G
通讯作者：
Eisenbrand G
影响因子：
10.3
作者：
SKEHAN, P;STORENG, R;BOYD, MR
通讯作者：
BOYD, MR
影响因子：
2.6
作者：
GEDIK, CM;EWEN, SWB;COLLINS, AR
通讯作者：
COLLINS, AR
影响因子：
2.7
作者：
GHOSAL, S;SINGH, SK;CHATTOPADHYAY, S
通讯作者：
CHATTOPADHYAY, S
I型和II型拓扑异构酶的细胞周期耦合搬迁以及催化酶活性的调节。
影响因子：
7.8
作者：
Meyer, KN;Kjeldsen, E;Straub, T;Knudsen, BR;Hickson, ID;Kikuchi, A;Kreipe, H;Boege, F
通讯作者：
Boege, F