Chikako Nakai
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21 Japan, Department of Intractable Diseases, International Medical Center of Japan, Shinjuku-ku, Tokyo 162-8655, Japan
Kohei Kamiya
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Toshiko Satake
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Isoko Kuriyama
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Hiroshi Iijima
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Hiroshi Ikawa
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Hiromi Yoshida
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan, 4High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
Yoshiyuki Mizushina
Faculty of Pharmaceutical Science, High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan, 4High Technology Research Center, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-21, Japan
ABSTRACT
Present study, isolated the parameritannins A-2 and A-3, new A-type tetrameric proanthocyanidins, from the bark of Parameria laerigata Moldenke and showed that they inhibited eukaryotic topos I, II or both activities in vitro. Although they are structurally isomeric compounds, their inhibitory effects against topos were different. Parameritannin A-2 only inhibited topo II activity with IC50 value of 0.5 μM, while parameritannin A-3 inhibited both topos I and II activities with IC50 values of 50 and 0.5 μM, respectively. The inhibitory actions of parameritannin A-3 against topos I and II were also different. Preincubation analysis suggests that parameritannin A-3 binds both topo I and substrate DNA and it has high binding affinity to DNA rather than topo I. Inhibitory activity against topo II was same for either pretreatment with enzyme or DNA. In addition, only parameritannin A-3 induced apoptosis although both parameritannins A-2 and A-3 arrested the cell cycle at G2/M phase. This is the first report that parameritannins act as topo inhibitors and present results further support its therapeutic potential as a leading anti-cancer compound that poisons topos.
PDF References
How to cite this article
Chikako Nakai, Kohei Kamiya, Toshiko Satake, Isoko Kuriyama, Hiroshi Iijima, Hiroshi Ikawa, Hiromi Yoshida and Yoshiyuki Mizushina, 2005. Novel Topoisomerase I and II Inhibitors, Parameritannins A-2 and A-3, are Selective Human Cancer Cytotoxins. International Journal of Pharmacology, 1: 138-151.
DOI: 10.3923/ijp.2005.138.151
URL: https://scialert.net/abstract/?doi=ijp.2005.138.151
DOI: 10.3923/ijp.2005.138.151
URL: https://scialert.net/abstract/?doi=ijp.2005.138.151
REFERENCES
- Chowdhury, A.R., S. Sharma, S. Mandel, A. Goswami, S. Mukhopadhyay and H.K. Majumder, 2002. Luteolin, an emerging anti-cancer flavonoid, poisons eukaryotic DNA topoisomerase I. Biochem. J., 366: 653-661.
Direct Link - Ahmad, N., D.K. Feyes, A.L. Nieminen, R. Agarwal and H. Mukhtar, 1997. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J. Natl. Cancer Inst., 89: 1881-1886.
CrossRefPubMedDirect Link - Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65: 55-63.
CrossRefPubMedDirect Link - Boege, F., T. Straub, A. Kehr, C. Bosenberg and K. Christiansen et al., 1996. Selected novel flavones inhibit the DNA binding or the DNA relegation step of eukaryotic topoisomerase I. J. Biol. Chem., 271: 2262-2270.
Direct Link - Kohn, E.A., N.D. Ruth, M.K. Brown, M. Livingstone and A. Eastman, 2002. Abrogation of the S phase DNA damage checkpoint results in S phase progression or premature mitosis depending on the concentration of 7-hydroxystaurosporine and the kinetics of Cdc25C activation. J. Biol. Chem., 277: 26553-26564.
- Granvile, D.J., C.M. Carthy, D.W.C. Hunt and B.M. McMabus, 1996. Apoptosis: Molecular aspects of cell death and disease. Lab. Invest., 78: 893-913.
Direct Link - Masson, M., C. Niedergang, V. Schreiber, S. Muller, J. Menissier-de-Murcia and G. de Murcia, 1998. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell Biol., 18: 3563-3571.
PubMedDirect Link - Kubota, Y., R.A. Nash, A. Klungland, P. Schar, D.E. Barnes and T. Lindahl, 1996. Reconstitution of DNA base excision-repair with purified human proteins: Interaction between DNA polymerase b and the XRCC1 protein. EMBO. J., 15: 6662-6670.
PubMedDirect Link - Vidal, A.E., S. Boiteux, I.D. Hickson and J.P. Radicella, 2001. XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. EMBO J., 20: 6530-6539.
Direct Link - Whitehouse, C.J., R.M. Taylor, A. Thistlethwaite, H.G. Zhang and F. Karimi-Busheri et al., 2001. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell, 104: 107-117.
CrossRefDirect Link - Froelich-Ammon, S.J. and N. Osheroff, 1995. Topoisomerase poisons: Harnessing the dark side of enzyme mechanism. J. Biol. Chem., 270: 21429-21432.
CrossRefDirect Link - Leteurtre, F., A. Fujimori, A. Tanizawa, A. Chhabra and A. Mazumder et al., 1994. Saintopin, a dual inhibitor of DNA topoisomerases I and II, as a probe for drug-enzyme interactions. J. Biol. Chem., 269: 28702-28707.
Direct Link - Riou, J.F., P. Fosse, C.H. Nguyen, A.K. Larsen and M.C. Bissery et al., 1993. Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents inhibiting both topoisomerase I and II activities. Cancer Res., 53: 5987-5993.
Direct Link - De Murcia, G. and J.M. de Murcia, 1994. Poly (ADP-ribose) polymerase: A molecular nick-sensor. Trends Biochem. Sci., 19: 172-176.
CrossRefDirect Link - Wei, Y.F., P. Robins, K. Carter, K. Caldecott and D.J.C. Pappin et al., 1995. Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Mol. Cell Biol., 15: 3206-3216.
CrossRefDirect Link - Dantzer, F., G. de Murcia, J. Menissier-de Murcia, H.P. Nasheuer and J.L. Vonesch, 1998. Functional association of poly (ADP-ribose) polymerase with DNA polymerase α-primase complex: A link between DNA strand break detection and DNA replication. Nucl. Acids Res., 26: 1891-1898.
CrossRefDirect Link - Yoshida, S. and C.M.G. Simblan, 1994. Interaction of poly (ADP-ribose) polymerase with DNA polymerase α. Mol. Cell Biochem., 138: 39-44.
CrossRef - Caldecott, K.W., S. Aoufouchi, P. Johnson and S. Shall, 1996. XRCC1 polypeptide interacts with DNA polymerase b and possibly poly (ADP-ribose) polymerase and DNA ligase III is a novel molecular nick-sensor in vitro. Nucleic Acids Res., 24: 4387-4394.
PubMedDirect Link - Nash, R.A., K.W. Caldecott, D.E. Barness and T. Lindahl, 1997. XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry, 36: 5207-5211.
CrossRefDirect Link - Lappard, J.B., Z. Dong, Z.B. Mackey and A.E. Tomkinson, 2003. Physical and functional interaction between DNA ligase IIIα and poly (ADP-ribose) polymerase 1 in DNA single-strand break repair. Mol. Cell. Biol., 23: 5919-5927.
CrossRefDirect Link - Bauer, P.I., K.G. Buki, J.A. Comstock and E. Kun, 2000. Activation of topoisomerase I by poly [ADP-ribose] polymerase. Int. J. Mol. Med., 5: 533-573.
Direct Link - Boothman, D.A., N. Fukunaga and M. Wang, 1994. Down-regulation of topoisomerase I in mammalian cells following ionizing radiation. Cancer Res., 54: 4618-4626.
Direct Link - Yung, T.M.C., M. Parent, E.L.Y. Ho and M.S. Satoh, 2004. Camptothecin-sensitive relaxation of supercoiled DNA by the topoisomerase I-like activity associated with poly (ADP-ribose) polymerase-1. J. Biol. Chem., 279: 11992-11999.
CrossRefDirect Link - Sabourin, M. and N. Osheroff, 2000. Sensitivity of human type II topoisomerases to DNA damage: Stimulation of enzyme-mediated DNA cleavage by abasic, oxidized and alkylated lesions. Nucl. Acid Res., 28: 1947-1954.
CrossRefDirect Link - Norbury, C.J. and I.D. Hickson, 2001. Cellular responses to DNA damage. Annu. Rev. Pharmacol. Toxicol., 41: 367-401.
CrossRefDirect Link