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Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.
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MedLine Citation:
PMID:  11720449     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 microM). The growth of human leukaemia cell lines was also potently inhibited (mean IC(50) = 1.3 microM). 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 II beta poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase II beta protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase II alpha protein was observed. In A431 cells immunoband-depletion of topoisomerase II beta 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.
Authors:
H U Barthelmes; E Niederberger; T Roth; K Schulte; W C Tang; F Boege; H H Fiebig; G Eisenbrand; D Marko
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of cancer     Volume:  85     ISSN:  0007-0920     ISO Abbreviation:  Br. J. Cancer     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-26     Completed Date:  2002-02-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370635     Medline TA:  Br J Cancer     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1585-91     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger Str. 52, 67663 Kaiserslautern, Germany.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / chemistry,  pharmacology*
Amaryllidaceae Alkaloids*
Animals
Antigens, Neoplasm
Antineoplastic Agents, Phytogenic / chemistry,  pharmacology*
Blotting, Western
Cell Cycle
Cell Division / drug effects
Comet Assay
DNA / metabolism
DNA Damage
DNA Topoisomerases, Type II / antagonists & inhibitors*,  immunology,  metabolism
DNA Topoisomerases, Type II, Eukaryotic / antagonists & inhibitors,  metabolism
DNA-Binding Proteins
Enzyme Inhibitors / chemistry,  pharmacology*
HL-60 Cells
Humans
Indolizines*
Mice
Mice, Nude
Neoplasms, Experimental / drug therapy*,  enzymology,  pathology
Tumor Cells, Cultured
Tumor Stem Cell Assay
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Amaryllidaceae Alkaloids; 0/Antigens, Neoplasm; 0/Antineoplastic Agents, Phytogenic; 0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/Indolizines; 2121-12-2/ungeremine; 9007-49-2/DNA; EC 5.99.1.-/DNA Topoisomerases, Type II, Eukaryotic; EC 5.99.1.3/DNA Topoisomerases, Type II; EC 5.99.1.3/DNA topoisomerase II alpha; EC 5.99.1.3/DNA topoisomerase II beta
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Br J Cancer
ISSN: 0007-0920
ISSN: 1532-1827
Publisher: Nature Publishing Group
Article Information
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Copyright 2001, Cancer Research Campaign
Received Day: 24 Month: 01 Year: 2001
Revision Received Day: 20 Month: 07 Year: 2001
Accepted Day: 24 Month: 08 Year: 2001
Print publication date: Month: 11 Year: 2001
Volume: 85 Issue: 10
First Page: 1585 Last Page: 1591
ID: 2363954
Publisher Item Identifier: 6692142
DOI: 10.1054/bjoc.2001.2142
PubMed Id: 11720449

Lycobetaine acts as a selective topoisomerase IIβ poison and inhibits the growth of human tumour cells
H U Barthelmes2
E Niederberger1
T Roth4
K Schulte1
W C Tang1
F Boege2
H-H Fiebig34
G Eisenbrand1
D Marko1
1Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger Str. 52, Kaiserslautern, 67663
2Medizinische Poliklinik, University of Würzburg Medical School, Klinikstr. 6–8, Würzburg, 97070
3Tumor Biology Center at the University of Freiburg, Breisacher Str. 117, Freiburg i. Br., 79106
4Institute for Experimental Oncology, Oncotest GmbH, Am Flughafen 8–10, Freiburg i. Br., 79110, Germany


Article Categories:
  • Regular Article

Keywords: lycobetaine, ungeremine, topoisomerase IIβ, cleavable complex, clonogenic assay, gastric carcinoma.

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