Share This Article:

Hypersensitive Inhibition of the Proliferation of Cells with Mutated DNA Repair-Related Genes by the Catalytic Topoisomerase II Inhibitor 20-O-IngenolEZ

Abstract Full-Text HTML XML Download Download as PDF (Size:709KB) PP. 158-165
DOI: 10.4236/pp.2012.32023    3,170 Downloads   6,100 Views   Citations

ABSTRACT

We previously reported that many ingenol compounds derived from Euphoria kansui exhibit topoisomerase inhibitory activity. 20-O-ingenolEZ in these compounds exerted inhibitory effects on both topoisomerase II (topo II) activity and cell proliferative activity. Topoisomerase II inhibitors can be divided into the poison and catalytic inhibitor types and 20-O-ingenolEZ is a catalytic inhibitor and inhibits topo IIα through inhibition of ATPase activity, but induces topo II-mediated DNA damage and apoptosis in BLM-/- DT40 cells through the induction of the DNA damage checkpoint, similar to the poison type inhibitor adriamycin. The ATPase inhibitor of topo II ICRF-193 also showed poison-like characteristics in the same cell line. However, the inhibitory effects of ICRF-193 on the proliferation of BLM-/- DT40 cells differed from those of 20-O-ingenolEZ, as did the specificity of its inhibition of the proliferation of other cell lines. 20-O-ingenolEZ showed hypersensitive inhibition of the proliferation of MCF-7 cells and BLM-/- DT40 cells with mutated DNA repair-related genes.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Kanbe, Y. Fukuda, M. Watanabe, K. Matsuzaki, S. Kitanaka and S. Miyata, "Hypersensitive Inhibition of the Proliferation of Cells with Mutated DNA Repair-Related Genes by the Catalytic Topoisomerase II Inhibitor 20-O-IngenolEZ," Pharmacology & Pharmacy, Vol. 3 No. 2, 2012, pp. 158-165. doi: 10.4236/pp.2012.32023.

References

[1] J. C. Wang, “Cellular ROLES OF DNA topoisomerases: a molecular perspective,” Nature Reviews Molecular Cell Biology, Vol. 3, No. 6, 2002, pp. 430-440. doi:10.1038/nrm831
[2] S. J. Froelich-Ammon and N. Osheroff, “Topoisomerase Poisons: Harnessing the Dark Side of Enzyme Mechanism,” Journal of Biological Chemistry, Vol. 270, No. 37, 1995, pp. 21429-21432. doi:10.1074/jbc.270.37.21429
[3] D. A. Burden and N. Osheroff, “Mechanism of Action of Eukaryotic Topoisomerase II and Drugs Targeted to the Enzyme,” Biochimica et Biophysica Acta, Vol. 1400, No. 1-3, 1998, pp. 139-154.
[4] T. Andoh and R. Ishida, “Catalytic inhibitors of DNA topoisomerase II,” Biochimica et Biophysica Acta, Vol. 1400, No. 1-3, 1998, pp. 155-171.
[5] A. K. Larsen, A. E. Escargueil and A. Skladanowski, “Catalytic Topoisomerase II Inhibitors in Cancer Therapy,” Pharmacology & Therapeutics, Vol. 99, No. 2, 2003, pp. 167-181. doi:10.1016/S0163-7258(03)00058-5
[6] J. Roca, R. Ishida and J. M. Berger, “Antitumor Bisdioxopiperazines Inhibit Yeast DNA Topoisomerase II by Trapping the Enzyme in the Form of a Closed Protein Clamp,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 5, 1994, pp.1781-1785. doi:10.1073/pnas.91.5.1781
[7] T. Hu, H. Sage and T. S. Hsieh, “ATPase Domain of Eukaryotic DNA Topoisomerase II. Inhibition of ATPase Activity by the Anti-Cancer Drug Bisdioxopiperazine and ATP/ADP-Induced Dimerization,” Journal of Biological Chemistry, Vol. 277, No. 8, 2002, pp. 5944-5951. doi:10.1074/jbc.M111394200
[8] M. S. Hossain, N. Akimitsu, T. Takaki, H. Hirai and K. Sekimizu, “ICRF-193, a Catalytic Inhibitor of DNA Topoisomerase II, Inhibits Re-Entry into the Cell Division Cycle from Quiescent State in Mammalian Cells,” Genes Cells, Vol. 7, No. 3, 2002, pp. 285-294. doi:10.1046/j.1365-2443.2002.00521.x
[9] M. Damelin and T. H. Bestor, “The Decatenation Checkpoint,” British Journal of Cancer, Vol. 96, No. 2, 2007, pp. 201-205. doi:10.1038/sj.bjc.6603537
[10] K. R. Hande, “Clinical Applications of Anticancer Drugs Targeted to Topoisomerase II,” Biochimica et Biophysica Acta, Vol. 1400, No. 1-3, 1998, pp. 173-184.
[11] W. E. Ross, D. Glaubiger and K. W. Kohn, “Qualitative and Quantitative Aspects of Intercalator-Induced DNA Strand Breaks,” Biochimica et Biophysica Acta, Vol. 562, No. 1, 1979, pp. 41-50.
[12] K. M. Tewey, T. C. Rowe, L. Yang, B. D. Halligan and L. F. Liu, “Adriamycin-Induced DNA Damage Mediated by Mammalian DNA Topoisomerase II,” Science, Vol. 226, No. 4673, 1984, pp. 466-468. doi:10.1126/science.6093249
[13] S. J. Haggarty, K. M. Koeller, T. R. Kau, P. A. Silver, M. Roberge and S. L. Schreiber, “Small Molecule Modulation of the Human Chromatid Decatenation Checkpoint,” Chemistry & Biology, Vol. 10, No. 12, 2003, pp. 1267-1279. doi:10.1016/j.chembiol.2003.11.014
[14] P. Chène, J. Rudloff, J. Schoepfer, P. Furet, P. Meier, Z. Qian, J. M. Schlaeppi, R. Schmitz and T. Radimerski, “Catalytic Inhibition of Topoisomerase II by a Novel Rationally Designed ATP-Competitive Purine Analogue,” BMC Chemical Biology, Vol. 9, No. 1, 2009, pp. 1-16. doi:10.1186/1472-6769-9-1
[15] C. Yoshida, K. Hishiyama, K. Miyazaki, M. Watanabe, M. Kanbe, Y. Yamada, K. Matsuzaki, K. Miyashita, S. Kitanaka and S. Miyata, “Analysis of Inhibition of Topoisomerase IIalpha and Cancer Cell Proliferation by IngenolEZ,” Cancer Science, Vol. 101, No. 2, 2010, pp. 374-378. doi:10.1111/j.1349-7006.2009.01408.x
[16] M. Watanabe, Y. Kamada, K. Miyazaki, S. Mizoguchi, K. Matsuzaki, S. Kitanaka and S. Miyata, “20-O-IngenolEZ, a Catalytic Topoisomerase II Inhibitor, Specifically Inhibits Cell Proliferation and Induces Double-Strand DNA Breaks in BLM-/- Cells,” Medicinal Chemistry Communications, Vol. 2, No. 9, 2011, pp. 824-827. doi:10.1039/c0md00252f
[17] N. Adachi, H. Suzuki, S. Iiizumi and H. Koyama, “Hypersensitivity of Nonhomo-logous DNA End-Joining Mutants to VP-16 and ICRF-193: Implications for the Repair of Topoisomerase II-Mediated DNA Damage,” Journal of Biological Chemistry, Vol. 278, No. 38, 2003, pp. 35897- 35902. doi:10.1074/jbc.M306500200
[18] C. Pérez, N. E. Vila-boa, L. García-Bermejo, E. de Blas, A. M. Creighton and P. Aller, “Differentiation of U-937 Promonocytic Cells by Etoposide and ICRF-193, Two Antitumour DNA Topoisomerase II Inhibitors with Different Mechanisms of Action,” Journal of Cell Science, Vol. 110, No. 3, 1997, pp. 337-343.
[19] T. Marple, T. M. Kim and P. Hasty, “Embryonic Stem Cells Deficient for Brca2 or Blm Exhibit Divergent Genotoxic Profiles That Support Opposing Activities during Homologous Recombination,” Mutation Research, Vol. 602, No. 1-2, 2006, pp. 110-120. doi:10.1016/j.mrfmmm.2006.08.005
[20] N. Pastor, I. Domínguez, S. Mateos and F. Cortés, “A Comparative Study of Genotoxic Effects of Anti-Topoisomerase II Drugs ICRF-193 and Bufalin in Chinese Hamster Ovary Cells,” Mutation Research, Vol. 515, No. 1-2, 2002, pp. 171-180.
[21] L. H. Jensen, K. C. Nitiss, A. Rose, J. Dong, J. Zhou, T. Hu, N. Osheroff, P. B. Jensen, M. Se-hested and J. L. Nitiss, “A Novel Mechanism of Cell Killing by Anti-Topoisomerase II Bisdioxopiperazines,” Journal of Biological Chemistry, Vol. 275, No. 3, 2000, pp. 2137-2146. doi:10.1074/jbc.275.3.2137
[22] M. Damelin, Y. E. Sun, V. B. Sodja and T. H. Bestor, “Decatenation Checkpoint Deficiency in Stem and Progenitor Cells,” Cancer Cell, Vol. 8, No. 6, 2005, pp. 479-484. doi:10.1016/j.ccr.2005.11.004
[23] A. Franchitto, J. Oshima and P. Pichierri, “The G2-Phase Decatenation Checkpoint Is Defective in Werner Syndrome Cells,” Cancer Research, Vol. 63, No. 12, 2003, pp. 3289-3295.
[24] T. Nakagawa, Y. Hayashita, K. Maeno, A. Masuda, N. Sugito, H. Osada, K. Yanagisawa, H. Ebi, K. Shimokata and T. Takahashi, “Identification of Decatenation G2 Checkpoint Impairment Independently of DNA Damage G2 Checkpoint in Human Lung Cancer Cell Lines,” Cancer Research, Vol. 64, No. 14, 2004, pp. 4826-4832. doi:10.1158/0008-5472.CAN-04-0871
[25] M.C. Alley, D.A. Scudiero, A. Monks, M. L. Hursey, M. J. Czerwinski, D. L. Fine, B. J. Abbott, J. G. Mayo, R. H. Shoemaker and M. R. Boyd, “Feasibility of Drug Screening with Panels of Human Tumor Cell Lines Using a Microculture Tetrazolium Assay,” Cancer Research, Vol. 48, No. 3, 1988, pp. 589-601.
[26] E. B. Cogan, G. B. Birrell and O. H. Griffith, “A Robotics-Based Automated Assay for In-organic and Organic Phosphates,” Analytical Biochemistry, Vol. 271, No. 1, 1999, pp. 29-35. doi:10.1006/abio.1999.4100
[27] E. P. Rogakou, D. R. Pilch and A. H. Orr, “DNA Double-Stranded Breaks In-duce Histone H2AX Phosphorylation on Serine 139,” Journal of Biological Chemistry, Vol. 273, No. 10, 1998, pp. 5858-5868. doi:10.1074/jbc.273.10.5858
[28] P. R. Andreassen, F. B. Lacroix and R. L. Margolis, “Chromosomes with Two Intact Axial Cores Are Induced by G2 Checkpoint Override: Evidence That DNA Decatenation Is Not Required to Template the Chromosome Structure,” Journal of Cell Biology, Vol. 136, No. 1, 1997, pp. 29-43. doi:10.1083/jcb.136.1.29
[29] C. S. Downes, D. J. Clarke, A. M. Mullinger, J. F. Giménez-Abián, A. M. Creighton and R. T. Johnson, “A Topoisomerase II-Dependent G2 Cycle Checkpoint in Mammalian Cells,” Nature, Vol. 372, No. 6505, 1994, pp. 467-470. doi:10.1038/372467a0
[30] P. B. Deming, C. A. Cistulli, H. Zhao, P. R. Graves, H. Piwnica-Worms, R. S. Paules, C. S. Downes and W. K. Kaufmann, “The Human Decatenation Checkpoint,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 21, 2001, pp. 12044-12049. doi:10.1073/pnas.221430898
[31] K. Luo, J. Yuan, J. Chen and Z. Lou, “Topoisomerase II Alpha Controls the Decatenation Checkpoint,” Nature Cell Biology, Vol. 11, No. 2, 2009, pp. 204-210. doi:10.1038/ncb1828
[32] I. Park and H. K. Avraham, “Cell Cycle-Dependent DNA Damage Signaling Induced by ICRF-193 Involves ATM, ATR, CHK2, and BRCA1,” Experimental Cell Research, Vol. 312, No. 11, 2006, pp. 1996-2008. doi:10.1016/j.yexcr.2006.02.029
[33] H. M. Robinson, S. Bratlie-Thoresen, R. Brown and D. A. Gillespie, “Chk1 Is Required for G2/M Checkpoint Response Induced by the Catalytic Topoisomerase II Inhibitor ICRF-193,” Cell Cycle, Vol. 6, No. 10, 2007, pp. 1265-1267. doi:10.4161/cc.6.10.4225
[34] A. Zhang, Y. L. Lyu, C. P. Lin, N. Zhou, A. M. Azarova, L. M. Wood and L. F. Liu, “A Protease Pathway for the Repair of Topoisomerase II-DNA Covalent Complexes,” Journal of Biological Chemistry, Vol. 281, No. 47, 2006, pp. 35997-36003. doi:10.1074/jbc.M604149200
[35] H. Xiao, Y. Mao, S.D. Desai, N. Zhou, C. Y. Ting, J. Hwang and L. F. Liu, “The Topoisomerase IIbeta Circular Clamp Arrests Transcription and Signals a 26S Proteasome Pathway,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 6, 2003, pp. 3239-3244. doi:10.1073/pnas.0736401100
[36] W. P. Roos and B. Kaina, “DNA Damage-Induced Cell Death by Apoptosis,” Trends in Molecular Medicine, Vol. 12, No. 9, 2006, pp. 440-450. doi:10.1016/j.molmed.2006.07.007
[37] L. Wu, S. L. Davies, N. C. Levitt and I. D. Hickson, “Potential Role for the BLM Helicase in Recombinational Repair via a Conserved Interaction with RAD51,” Journal of Biological Chemistry, Vol. 276, No. 22, 2001, pp. 19375-19381. doi:10.1074/jbc.M009471200
[38] S. L. Ding, J. C. Yu, S. T. Chen, G. C. Hsu, S. J. Kuo, Y. H. Lin, P. E. Wu and C. Y. Shen, “Genetic Variants of BLM Interact with RAD51 to Increase Breast Cancer Susceptibility,” Carci-nogenesis, Vol. 30, No. 1, 2009, pp. 43-49. doi:10.1093/carcin/bgn233
[39] O. S. Gildemeister, J. M. Sage and K. L. Knight, “Cellular Redistribution of Rad51 in Response to DNA Damage: Novel Role for Rad51C,” Journal of Biological Chemistry, Vol. 284, No. 46, 2009, pp. 31945-31952. doi:10.1074/jbc.M109.024646
[40] O. A. Hampton, P. Den Hollander, C. A. Miller, D. A. Delgado, J. Li, C. Coarfa, R. A. Harris, S. Richards, S. E. Scherer, D. M. Muzny, R. A. Gibbs, A. V. Lee and A. Milosavljevic, “A Sequence-Level Map of Chromosomal Breakpoints in the MCF-7 Breast Cancer Cell Line Yields Insights into the Evolution of a Cancer Genome,” Genome Research, Vol. 19, No. 2, 2009, pp. 167-177. doi:10.1101/gr.080259.108
[41] Y. Zheng, J. Zhang, K. Hope, Q. Niu, D. Huo and O. I. Olopade, “Screening RAD51C Nucleotide Alterations in Patients with a Family History of Breast and Ovarian Cancer,” Breast Cancer Research and Treatment, Vol. 124, No. 3, 2010, pp. 857-861. doi:10.1007/s10549-010-1095-5
[42] Y. Yarden and M. X. Sliwkowski, “Untangling the ErbB Signalling Network,” Nature Reviews Molecular Cell Biology, Vol. 2, No. 2, 2001, pp. 127-137. doi:10.1038/35052073
[43] A. Meindl, H. Hellebrand, C. Wiek, V. Erven, B. Wappenschmidt, D. Niederacher, M. Freund, P. Lichtner, L. Hartmann, H. Schaal, J. Ramser, E. Honisch, C. Kubisch, H.E. Wichmann, K. Kast, H. Deissler, C. Engel, B. Müller-Myhsok, K. Neveling, M. Kiechle, C. G. Mathew, D. Schindler, R. K. Schmutzler and H. Hanenberg, “Germline Mutations in Breast and Ovarian Cancer Pedigrees Establish RAD51C as a Human Cancer Susceptibility Gene,” Nature Genetics, Vol. 42, No. 5, 2010, pp. 410-414. doi:10.1038/ng.569

  
comments powered by Disqus

Copyright © 2019 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.