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Archives of Pharmacal Research

, Volume 35, Issue 10, pp 1849–1854 | Cite as

Pharmacokinetics and tissue distribution of psammaplin A, a novel anticancer agent, in mice

  • Hak Jae Kim
  • Tae Hwan Kim
  • Won Sik Seo
  • Sun Dong Yoo
  • Il Han Kim
  • Sang Hoon Joo
  • Soyoung Shin
  • Eun-Seok Park
  • Eun Sook Ma
  • Beom Soo ShinEmail author
Research Article Drug Actions

Abstract

This study reports the pharmacokinetics and tissue distribution of a novel histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in mice. PsA concentrations were determined by a validated LC-MS/MS assay method (LLOQ 2 ng/mL). Following intravenous injection at a dose of 10 mg/kg in mice, PsA was rapidly eliminated, with the average half-life (t1/2, λn) of 9.9 ± 1.4 min and the systemic clearance (CLs) of 925.1 ± 570.1 mL/min. The in vitro stability of PsA was determined in different tissue homogenates. The average degradation t1/2 of PsA in blood, liver, kidney and lung was found relatively short (≤ 12.8 min). Concerning the in vivo tissue distribution characteristics, PsA was found to be highly distributed to lung tissues, with the lung-to-serum partition coefficients (Kp) ranging from 49.9 to 60.2. In contrast, PsA concentrations in other tissues were either comparable with or less than serum concentrations. The high and specific lung targeting characteristics indicates that PsA has the potential to be developed as a lung cancer treatment agent.

Key words

Psammaplin A Pharmacokinetics Tissue distribution Stability 

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References

  1. Ahn, M. Y., Jung, J. H., Na, Y. J., and Kim, H. S., A natural histone deacetylase inhibitor, Psammaplin A, induces cell cycle arrest and apoptosis in human endometrial cancer cells. Gynecol. Oncol., 108, 27–33 (2008).PubMedCrossRefGoogle Scholar
  2. Arabshahi, L. and Schmitz, F. J., Brominated tyrosine metabolites from an unidentified sponge. J. Org. Chem., 52, 3584–3586 (1987).CrossRefGoogle Scholar
  3. Brown, R. P., Delp, M. D., Lindstedt, S. L., Rhomberg, L. R., and Beliles, R. P., Physiological parameter values for physiologically based pharmacokinetic models. Toxicol. Ind. Health, 13, 407–484 (1997).PubMedGoogle Scholar
  4. Davie, J. R., Covalent modifications of histones: expression from chromatin templates. Curr. Opin. Genet. Dev., 8, 173–178 (1998).PubMedCrossRefGoogle Scholar
  5. Egger, G., Liang, G., Aparicio, A., and Jones, P. A., Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429, 457–463 (2004).PubMedCrossRefGoogle Scholar
  6. Esteller, M., Relevance of DNA methylation in the management of cancer. Lancet Oncol., 4, 351–358 (2003).PubMedCrossRefGoogle Scholar
  7. Fouladi, M., Histone deacetylase inhibitors in cancer therapy. Cancer Invest., 24, 521–527 (2006).PubMedCrossRefGoogle Scholar
  8. Glozak, M. A. and Seto, E., Histone deacetylases and cancer. Oncogene, 26, 5420–5432 (2007).PubMedCrossRefGoogle Scholar
  9. Grignani, F., De, Matteis, S., Nervi, C., Tomassoni, L., Gelmetti, V., Cioce, M., Fanelli, M., Ruthardt, M., Ferrara, F. F., Zamir, I., Seiser, C., Grignani, F., Lazar, M. A., Minucci, S., and Pelicci, P. G., Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature, 391, 815–818 (1998).PubMedCrossRefGoogle Scholar
  10. Jones, P. A. and Baylin, S. B., The fundamental role of epigenetic events in cancer. Nat. Rev. Genet., 3, 415–428 (2002).PubMedCrossRefGoogle Scholar
  11. Kim, D., Lee, I. S., Jung, J. H., Lee, C. O., and Choi, S. U., Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells. Anticancer Res., 19, 4085–4090 (1999a).PubMedGoogle Scholar
  12. Kim, D., Lee, I. S., Jung, J. H., and Yang, S. I., Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillinresistant Staphylococcus aureus and the DNA gyraseinhibitory activity. Arch. Pharm. Res., 22, 25–29 (1999b).PubMedCrossRefGoogle Scholar
  13. Kim, D. H., Shin, J., and Kwon, H. J., Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. Exp. Mol. Med., 28, 47–55 (2007).Google Scholar
  14. Kim, H. J., Kim, J. H., Chie, E. K., Young, P. D., Kim, I. A., and Kim, I. H., DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity. Radiat. Oncol., 7, 39–48 (2012).PubMedCrossRefGoogle Scholar
  15. Litterst, C. L., Mimnaugh, E. G., Reagan, R. L., and Gram, T. E., Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species. Drug Metab. Dispos., 3, 259–265 (1975).PubMedGoogle Scholar
  16. Nan, X., Ng, H. H, Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., and Bird, A., Transcriptional repression by methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature, 393, 386–389 (1998).PubMedCrossRefGoogle Scholar
  17. Nicholas, G. M., Eckman, L. L., Ray, S., Hughes, R. O., Pfefferkorn, J. A., Barluenga, S., Nicolaou, K. C., and Bewley, C. A., Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase. Bioorg. Med. Chem. Lett., 12, 2487–2490 (2002).PubMedCrossRefGoogle Scholar
  18. Park, Y., Liu, Y., Hong, J., Lee, C.-O., Cho, H., Kim, D.-K., Im, K. S., and Jung, J. H., New bromotyrosine derivatives from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis. J. Nat. Prod., 66, 1495–1498 (2003).PubMedCrossRefGoogle Scholar
  19. Piña, I. C., Gautschi, J. T., Wang, G. Y., Sanders, M. L., Schmitz, F. J., France, D., Cornell-Kennon, S., Sambucetti, L. C., Remiszewski, S. W., Perez, L. B., Bair, K. W., and Crews, P., Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J. Org. Chem., 68, 3866–3873 (2003).PubMedCrossRefGoogle Scholar
  20. Shin, J., Lee, H. S., Seo, Y., Rho, J. R., Cho, K. W., and Paul, V. J., New bromotyrosine metabolites from the sponge Aplysinella rhax. Tetrahedron, 56, 9071–9077 (2000).CrossRefGoogle Scholar
  21. Tabudravu, J. N., Eijsink, V. G., Gooday, G. W., Jaspars, M., Komander, D., Legg, M., Synstad, B., and van, Aalten, D. M., Psammaplin A, a chitinase inhibitor isolated from the Fijian marine sponge Aplysinella rhax. Bioorg. Med. Chem., 10, 1123–1128 (2002).PubMedCrossRefGoogle Scholar
  22. Watt, F. and Molloy, P. L., Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev., 2, 1136–1143 (1988).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Hak Jae Kim
    • 1
  • Tae Hwan Kim
    • 2
  • Won Sik Seo
    • 3
  • Sun Dong Yoo
    • 2
  • Il Han Kim
    • 1
  • Sang Hoon Joo
    • 3
  • Soyoung Shin
    • 4
  • Eun-Seok Park
    • 2
  • Eun Sook Ma
    • 3
  • Beom Soo Shin
    • 3
    Email author
  1. 1.Department of Radiation OncologySeoul National University HospitalSeoulKorea
  2. 2.School of PharmacySungkyunkwan UniversitySuwonKorea
  3. 3.College of PharmacyCatholic University of DaeguGyeongsanKorea
  4. 4.College of PharmacyWonkwang UniversityIksanKorea

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