The Topopyrones Poison Human DNA Topoisomerases I and II

2008 ◽  
Vol 130 (39) ◽  
pp. 12888-12889 ◽  
Author(s):  
Qasim A. Khan ◽  
Mark A. Elban ◽  
Sidney M. Hecht
Keyword(s):  
Dna Topoisomerases ◽  
Human Dna

Antitumor Effect of Pomolic Acid in Acute Myeloid Leukemia Cells Involves Cell Death, Decreased Cell Growth and Topoisomerases Inhibition

2019 ◽  
Vol 18 (10) ◽  
pp. 1457-1468
Author(s):  
Michelle X.G. Pereira ◽  
Amanda S.O. Hammes ◽  
Flavia C. Vasconcelos ◽  
Aline R. Pozzo ◽  
Thaís H. Pereira ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Acute Myeloid Leukemia ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Natural Compound ◽  
Dna Topoisomerases ◽  
Human Dna ◽  
Pomolic Acid ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML) represents the largest number of annual deaths from hematologic malignancy. In the United States, it was estimated that 21.380 individuals would be diagnosed with AML and 49.5% of patients would die in 2017. Therefore, the search for novel compounds capable of increasing the overall survival rate to the treatment of AML cells is urgent. Objectives: To investigate the cytotoxicity effect of the natural compound pomolic acid (PA) and to explore the mechanism of action of PA in AML cell lines with different phenotypes. Methods: Three different AML cell lines, HL60, U937 and Kasumi-1 cells with different mechanisms of resistance were used to analyze the effect of PA on the cell cycle progression, on DNA intercalation and on human DNA topoisomerases (hTopo I and IIα) in vitro studies. Theoretical experiments of the inhibition of hTopo I and IIα were done to explore the binding modes of PA. Results: PA reduced cell viability, induced cell death, increased sub-G0/G1 accumulation and activated caspases pathway in all cell lines, altered the cell cycle distribution and inhibited the catalytic activity of both human DNA topoisomerases. Conclusion: Finally, this study showed that PA has powerful antitumor activity against AML cells, suggesting that this natural compound might be a potent antineoplastic agent to improve the treatment scheme of this neoplasm.

Anthocyanidins Modulate the Activity of Human DNA Topoisomerases I and II and Affect Cellular DNA Integrity

2005 ◽  
Vol 18 (9) ◽  
pp. 1395-1404 ◽  
Author(s):  
Michael Habermeyer ◽  
Jessica Fritz ◽  
Hans U. Barthelmes ◽  
Morten O. Christensen ◽  
Morten K. Larsen ◽  
...  
Keyword(s):  
Dna Integrity ◽  
Dna Topoisomerases ◽  
Human Dna ◽  
Cellular Dna

Human DNA topoisomerases IIα and IIβ can functionally substitute for yeast TOP2 in chromosome segregation and recombination

1996 ◽  
Vol 252 (1-2) ◽  
pp. 79-86 ◽  
Author(s):  
Sanne Jensen ◽  
Charles S. Redwood ◽  
John R. Jenkins ◽  
Anni H. Andersen ◽  
Ian D. Hickson
Keyword(s):  
Chromosome Segregation ◽  
Dna Topoisomerases ◽  
Human Dna

DNA Binding by Fagaronine and Ethoxidine, Inhibitors of Human DNA Topoisomerases I and II, Probed by SERS and Flow Linear Dichroism Spectroscopy†

1999 ◽  
Vol 103 (11) ◽  
pp. 2008-2013 ◽  
Author(s):  
Anatoli Ianoul ◽  
Fabrice Fleury ◽  
Olivier Duval ◽  
Roger Waigh ◽  
Jean-Claude Jardillier ◽  
...  
Keyword(s):  
Dna Binding ◽  
Linear Dichroism ◽  
Dna Topoisomerases ◽  
Human Dna

New spiro-acridines: DNA interaction, antiproliferative activity and inhibition of human DNA topoisomerases

2016 ◽  
Vol 92 ◽  
pp. 467-475 ◽  
Author(s):  
Sinara Mônica Vitalino de Almeida ◽  
Elizabeth Almeida Lafayette ◽  
Willams Leal Silva ◽  
Vanessa de Lima Serafim ◽  
Thais Meira Menezes ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Dna Interaction ◽  
Dna Topoisomerases ◽  
Human Dna

scholarly journals Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase

2000 ◽  
Vol 350 (3) ◽  
pp. 757-763 ◽  
Author(s):  
Yoshiyuki MIZUSHINA ◽  
Akira IIDA ◽  
Keisuke OHTA ◽  
Fumio SUGAWARA ◽  
Kengo SAKAGUCHI
Keyword(s):  
Ursolic Acid ◽  
Dna Polymerase ◽  
Dna Polymerases ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dna Topoisomerases ◽  
Deoxyribonuclease I ◽  
Human Dna ◽  
Dna Binding Sites ◽  
Human Telomerase

As described previously, we found that new triterpenoid compounds, designated fomitellic acids A and B, which selectively inhibit the activities of mammalian DNA polymerases α and β [Mizushina, Tanaka, Kitamura, Tamai, Ikeda, Takemura, Sugawara, Arai, Matsukage, Yoshida and Sakaguchi (1998) Biochem. J. 330, 1325–1332; Tanaka, Kitamura, Mizushina, Sugawara and Sakaguchi (1998) J. Nat. Prod. 61, 193–197] and that a known triterpenoid, ursolic acid, is an inhibitor of human DNA topoisomerases I and II (A. Iida, Y. Mizushina and K. Sakaguchi, unpublished work). Here we report that all of these triterpenoids are potent inhibitors of calf DNA polymerase α, rat DNA polymerase β and human DNA topoisomerases I and II, and show moderate inhibitory effects on plant DNA polymerase II and human immunodeficiency virus reverse transcriptase. However, these compounds did not influence the activities of prokaryotic DNA polymerases such as Escherichia coli DNA polymerase I or other DNA metabolic enzymes such as human telomerase, T7 RNA polymerase and bovine deoxyribonuclease I. These triterpenoids were not only mammalian DNA polymerase inhibitors but also inhibitors of DNA topoisomerases I and II even though the enzymic characteristics of DNA polymerases and DNA topoisomerases, including their modes of action, amino acid sequences and three-dimensional structures, differed markedly. These triterpenoids did not bind to DNA, suggesting that they act directly on these enzymes. Because the three-dimensional structures of fomitellic acids were shown by computer simulation to be very similar to that of ursolic acid, the DNA-binding sites of both enzymes, which compete for the inhibitors, might be very similar. Fomitellic acid A and ursolic acid prevented the growth of NUGC cancer cells, with LD50 values of 38 and 30µM respectively.

Inhibitory effect of conjugated eicosapentaenoic acid on human DNA topoisomerases I and II

2005 ◽  
Vol 435 (1) ◽  
pp. 197-206 ◽  
Author(s):  
Yuko Yonezawa ◽  
Tsuyoshi Tsuzuki ◽  
Takahiro Eitsuka ◽  
Teruo Miyazawa ◽  
Takahiko Hada ◽  
...  
Keyword(s):  
Eicosapentaenoic Acid ◽  
Inhibitory Effect ◽  
Dna Topoisomerases ◽  
Human Dna

Human DNA topoisomerases IIα and IIβ can functionally substitute for yeastTOP2 in chromosome segregation and recombination

1996 ◽  
Vol 252 (1-2) ◽  
pp. 79-86 ◽  
Author(s):  
Sanne Jensen ◽  
Charles S. Redwood ◽  
John R. Jenkins ◽  
Anni H. Andersen ◽  
Ian D. Hickson
Keyword(s):  
Chromosome Segregation ◽  
Dna Topoisomerases ◽  
Human Dna

Effects of Camptothecin Analogues on DNA Transformations Mediated by Calf Thymus and Human DNA Topoisomerases I

1998 ◽  
Vol 11 (11) ◽  
pp. 1352-1360 ◽  
Author(s):  
Xiangyang Wang ◽  
Glenn F. Short ◽  
William D. Kingsbury ◽  
Randall K. Johnson ◽  
Sidney M. Hecht
Keyword(s):  
Dna Topoisomerases ◽  
Human Dna ◽  
Calf Thymus ◽  
Camptothecin Analogues
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