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Inhibition of DNA topoisomerases I and II of compounds from Reynoutria japonica

Abstract

Three anthraquinones (1, 2 and 4), three stilbenes (5, 6 and 7) and 3,5-dihydroxybenzyl alcohol (3) were isolated from Reynoutria japonica. Their structures were identified as emodin (1), emodin-8-O-β-d-glucoside (2), 3,5-dihydroxybenzyl alcohol (3), citreorosein (4), cis-resveratrol (5), trans-resveratrol (6) and trans-resveratrol-5-O-β-d-glucopyranoside (7) by comparing their physicochemical and spectral data with published data. Compound 3 was isolated for the first time from the Polygonaceae family. Among the purified compounds, 3 showed more potent inhibitory activity against topoisomerase I (IC50: 4 μM) than camptothecin, as the positive control (IC50: 18 μM). Compounds 3, 4, 5, 6 and 7 showed stronger inhibitory activities toward DNA topoisomerase II (IC50: 0.54, 14, 15, 0.77 and 3 μM, respectively) than the positive control, etoposide (IC50: 44 μM). Compounds 1 and 4 displayed weak cytotoxicities against human lung cancer (A549), ovarian cancer (SK-OV-3), human liver hepatoblastoma (HepG2) and colon adenocarcinoma (HT-29) cell lines.

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References

  • Bachmann, M., Blaser, P., Luthy, J., and Schlatter, C., Toxicity and mutagenicity of anthraquinones from Aspergillus chevalieri. J. Environ. Pathol. Toxicol. Oncol., 11, 49–52 (1992)

    PubMed  CAS  Google Scholar 

  • Bae, G. H., The Medicinal Plants of Korea, Kyo-Hak Publishing Co., Ltd., Seoul, p.161, (2000).

    Google Scholar 

  • Bosch, R., Friederich, U., Lutz, W. K., Brocker, E., and Bachmann, M., Investigations on DNA binding in rat liver and in Salmonella and on mutagenicity in the Ames test by emodin, a natural anthraquinone. Mutat. Res., 188, 161–168 (1987)

    PubMed  Article  CAS  Google Scholar 

  • Bourrier, O. and Kakkar, A. K., Dendritic polymers containing a dimethylsilyl linked dihydroxybenzyl alcohol backbone: divergent synthesis, aggregation, functionalization, and an evaluation of their applications in catalysis. J. Mater. Chem., 13, 1306–1315 (2003).

    Article  CAS  Google Scholar 

  • Burns, J., Yokota, Y., Ashihara, H., Lean, M. E. J., and Crozier, A., Plant foods and herbal sources of resveratrol. J. Agric. Food Chem., 50, 3337–3340 (2002).

    PubMed  Article  CAS  Google Scholar 

  • Chen, A. Y. and Liu, L. F., DNA topoisomerase: essential enzymes and lethal targets. Annu. Rev. Pharmacol. Toxicol., 34, 191–218 (1994).

    PubMed  Article  CAS  Google Scholar 

  • D’Arpa, P. and Liu, L. F., Topoisomerase-targeting antitumor drugs. Biochim. Biophys. Acta, 989, 163–177 (1989).

    PubMed  Google Scholar 

  • Demirezer, L. Ö., Kuruüzüm-Uz, A., Bergere, I., Schiewe, H. J., and Zeeck, A., The structures of antioxidant and cytotoxic agents from natural source: anthraquinones and tannins from roots of Rumex patientia. Phytochemistry, 58, 1213–1217 (2001).

    PubMed  Article  CAS  Google Scholar 

  • Fukuda, M., Nishio, K., Kanzawa, F., Ogasawara, H., Ishida, T., Arioka, H., Bojamowski, K., Oka, M., and Saijo, N., Synergism between cisplatin and topoisomerase I inhibitors, NB-506 and SN-38, in human small cell lung cancer cells. Cancer Res., 56, 789–793 (1996).

    PubMed  CAS  Google Scholar 

  • Fulvio, M., Fabiano, R., and Siegfried, K., Isolation, characterization, and evolution in red wine vinification of resveratrol monomers. J. Agric. Food Chem., 43, 1820–1823 (1995).

    Article  Google Scholar 

  • Gamini, S. J., Hiranthi, J., Lee, E. S., Koonchanok, N. M., Robert, L. G, Curtis, L. A., Jerry L. M., and Chang, C. J., Kinase inhibitors from Polygonum cuspidatum. J. Nat. Prod., 56, 1805–1810 (1993).

    Article  Google Scholar 

  • Hanawa, F., Tahara, S., and Nizutani, J., Antifungal stress compounds from Veratrum grandiflorum leaves treated with cupric chloride. Phytochemistry, 31, 3005–3007 (1992).

    Article  CAS  Google Scholar 

  • Hwang, H. Q., Li, H. L., Tang, J., Lv, W. P., and Zhang, W. D., A new aurone and other phenolic constituents from Veratrum schindleri Loes. F. Biochem. Syst. Ecol., 36, 590–592 (2008).

    Article  Google Scholar 

  • Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., and Thomas, C. F., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275, 218–220 (1997)

    PubMed  Article  CAS  Google Scholar 

  • Jayasuriya, H., Koonchanok, N. M., Geahlen, R. L., McLaughlin, J. L., and Chang, C. J., Emodin, a protein tyrosine kinase inhibitor from Polygonum cuspidatum. J. Nat. Prod., 55, 696–698 (1992)

    PubMed  Article  CAS  Google Scholar 

  • Jayatilake, G. S., Jayasuriya, H., Lee, E. S., Koonchanok, N. M., and Geahlen, R. L., Kinase inhibitors from Polygonum cuspidatum. J. Nat. Prod., 56, 1805–1810 (1993)

    PubMed  Article  CAS  Google Scholar 

  • Lee, C. H., Kim, S. L., Lee, K. B., Yoo, Y. C., Ryu, S. Y., and Son, K. S., Neuraminidase inhibitors from Reynoutria elliptica. Arch. Pharm. Res., 26, 367–374 (2003).

    PubMed  Article  CAS  Google Scholar 

  • Lee, Y. N., Flora of Korea. Kyo-Hak Publishing Co., Ltd., Seoul, p.114, (1996).

    Google Scholar 

  • Lin, S. Y., Lai, W. W., Ho, C. C., Yu, F. S., and Chen, G. W., Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways. Anticancer Res., 29, 327–335 (2009)

    PubMed  CAS  Google Scholar 

  • Liu, L. F., DNA topoisomerase poisons as antitumor drugs. Annu. Rev. Biochem., 58, 351–375 (1989).

    PubMed  Article  CAS  Google Scholar 

  • Ma, W. L., Yan, C. Y., Zhu, J. H., Duan, G. Y., and Yu, R. M., Biotransformation of paeonol and emodin by transgenic crown galls of Panax quinquefolium. Appl. Biochem. Biotechnol., 160, 1301–19308 (2010).

    PubMed  Article  CAS  Google Scholar 

  • Marquis, J. F., Markhey, D., LaVole, E. J., and Olivier, M., Effects of topoisomerases inhibitors protoberberine on Leishmania donovani growth, macrophage function and infection. J. Parasitol., 89, 1040–1052 (2003).

    Article  Google Scholar 

  • Matsuda, H., Shimoda, H., Morikawa, T., and Yoshikawa, M., Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure-requirement of hydroxyanthraquinones for estrogenic activity. Bioorg. Med. Chem. Lett., 11, 1839–1842 (2001)

    PubMed  Article  CAS  Google Scholar 

  • Mattivi, F., Reniero, F., and Korhammer, S., Isolation, characterization, and evolution in red wine vinification of resveratrol monomers. J. Agric. Food Chem., 43, 1820–1823 (1995).

    Article  CAS  Google Scholar 

  • Mittra, B., Saha, A., Chowdhury, A. R., Pal, C., Mandal, S., Mukhopadhyay, S., Bandyopadhyay, S., and Majumder, H. K., Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis. Mol. Med., 6, 527–541 (2000).

    PubMed  Article  CAS  Google Scholar 

  • Mueller, S. O. and Stopper, H., Characterization of the genotoxicity of anthraquinones in mammalian cells. Biochim. Biophys. Acta, 1428, 406–414 (1999)

    PubMed  Article  CAS  Google Scholar 

  • Na, M. G., Jin, W. Y., Min, B. S., Ahn, J, S., and Bae, K. H., Protein tyrosine phosphatase 1B inhibitory activity of anthraquinones and stilbenes. Nat. Prod. Sci., 14, 143–146 (2008).

    CAS  Google Scholar 

  • Nitiss, J. L., Targeting DNA topoisomerase II in cancer chemotherapy. Nat. Rev. Cancer, 9, 338–350 (2009).

    PubMed  Article  CAS  Google Scholar 

  • Pommier, Y., DNA topoisomerase I and II in cancer chemotherapy: update and perspectives. Cancer Chemother. Pharmacol., 32, 103–108 (1993).

    PubMed  Article  CAS  Google Scholar 

  • Pommier, Y., Topoisomerase I inhibitors: camptothecins and beyond. Nat. Rev. Cancer, 6, 789–802 (2006).

    PubMed  Article  CAS  Google Scholar 

  • Potmesil, M., Camptothecins: from bench research to hospital wards. Cancer Res., 54, 1431–1439 (1994).

    PubMed  CAS  Google Scholar 

  • Ray, S., Hazra, B., Mittra, B., Das, A., and Majumder, H. K., Diospyrin, a bisnapthoquinone: a novel inhibitor of type I DNA topoisomerase of Leishmania donovani. Mol. Pharmacol., 54, 994–999 (1998).

    PubMed  CAS  Google Scholar 

  • Ren, H., Gu, Q., and Zhu, W., Secalonic acid D; A cytotoxic constituent from marine lichen-derived fungus Gliocladium sp. T3. Arch. Pharm. Res., 29, 59–63 (2006).

    PubMed  Article  CAS  Google Scholar 

  • Rubinstein, L. V., Shoemaker, R. H., Paul, K. D., Simon, R. M., Tosini, S., Skehan, P., Scudiero, D. A., Monks, A., and Boyd, M. R., Comparison of in vitro anticancer-drug-screening data generated with a lines. J. Nat. Cancer Inst., 82, 1113–1118 (1990).

    PubMed  Article  CAS  Google Scholar 

  • Shen, M. Y., Liu Y. J., Don, M. J., Liu, H. Y., and Chen, Z. W., Combined phytochemistry and chemotaxis assays for identification and mechanistic analysis of antiinflammatory phytochemicals in Fallopia japonica. J. Agric. Food Chem., 48, 253–256 (2011)

    Google Scholar 

  • Slichenmyer, W. J., Rowinsky, E. K., Donehower, R. C., and Kaufmann, S. H., The current status of camptothecin analogues as antitumor agents. J. Natl. Cancer Inst., 85, 271–291 (1993).

    PubMed  Article  CAS  Google Scholar 

  • Vastano, B. C., Chen, Y., Zhu, N., Ho, C. T., Zhou, Z., and Rosen, R. T., Isolation and identification of stilbenes in two varieties of Polygonum cuspidatum. J. Agric. Food Chem., 48, 253–256 (2000)

    PubMed  Article  CAS  Google Scholar 

  • Walker, J. V. and Nitiss, J. L., DNA topoisomerase II as a target for cancer chemotherapy. Cancer Invest., 20, 570–589 (2002).

    PubMed  Article  CAS  Google Scholar 

  • Wang, J. C., DNA topoisomerases. Annu. Rev. Biochem., 65, 635–692 (1996).

    PubMed  Article  CAS  Google Scholar 

  • Xiao, K., Xuan, L., Xu, Y., Bai, D., and Zhong, D., Constituents from Polygonum cuspidatum. Chem. Pharm. Bull., 50, 605–608 (2002)

    PubMed  Article  CAS  Google Scholar 

  • Xu, M. L., Zheng, M. S., Lee, Y. K., Moon, D. C., Lee, C. S., Woo, M. H., Jeong, B. S., Lee, E. S., Jahng, Y., Chang, H. W., Lee, S. H., and Son, J. K., A New stilbene glucoside from the roots of Polygonum multiflorum Thunb. Arch. Pharm. Res., 29, 946–951 (2006)

    PubMed  Article  CAS  Google Scholar 

  • Yamada, M., Hayashi, K. I., Ikeda, S., Tsutsui, K., Tsutsui, K., Ito, T., Iinuma, M., and Nozaki, H., Inhibitory activity of plant stilbene oligomers against DNA topoisomerase II. Biol. Pharm. Bull., 29, 1504–1507 (2006)

    PubMed  Article  CAS  Google Scholar 

  • Yu, B. C., Yang, M. C., Lee, K. H., Kim, K. H., Choi, S. U., and Lee, K. R., Two new phenolic constituents of Humulus japonicus and their cytotoxicity test in vitro. Arch. Pharm. Res., 30, 1471–1475 (2007).

    PubMed  Article  CAS  Google Scholar 

  • Zhang, C., Wang, X., Zhang, X., Zhang, Y., and Xiao, H., Bioassay-guided separation of citreorosein and other oestrogenic compounds from Polygonum cuspidatum. Phytother. Res., 23, 740–741 (2009)

    PubMed  Article  CAS  Google Scholar 

  • Zhang, L., Lau, Y. K., Xi, L., Hong, R. L., and Kim, D. S., Tyrosine kinase inhibitors, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene, 16, 2855–2863 (1998)

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Jong-Keun Son.

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Thess authors contributed equally to this work.

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Hwangbo, K., Zheng, M.S., Kim, YJ. et al. Inhibition of DNA topoisomerases I and II of compounds from Reynoutria japonica . Arch. Pharm. Res. 35, 1583–1589 (2012). https://doi.org/10.1007/s12272-012-0909-x

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  • DOI: https://doi.org/10.1007/s12272-012-0909-x

Key words

  • Reynoutria japonica
  • Polygonaceae
  • Topoisomerase
  • Cytotoxicity