Advertisement

Isolation ofepi-oleanolic acid from korean mistletoe and its apoptosis-lnducing activity in tumor cells

  • Myung Ju Jung
  • Yung Choon Yoo
  • Kyung Bok Lee
  • Jong Bae Kim
  • Kyung Sik SongEmail author
Research Articles Articles

Abstract

A triterpene was isolated as a cytotoxic principle from the dichloromethane extract of Korean mistletoe (KM;Viscum album coloratum) by repeated silica gel chromatography and recrystallization. Inin vitro analysis of cytotoxic activity using various human and murine tumor cell lines, the dichloromethane extract of KM was highly cytotoxic against these cells. We isolated the most active compound, referred to VD-3, from the dichloromethane extract of KM. The VD-3 was shown to be less cytotoxic to normal cells (murine splenocytes). From the identification of the chemical structure of VD-3 by spectral data and chemical synthesis, the compound was proven to beepi-oleanolic acid. Tumor cells treated with VD-3 showed a typical pattern of apoptotic cell death, such as apparent morphological changes and DNA fragmentation. These results indicate thatepi-oleanolic acid is an important compound responsible for antitumor activity of KM.

Key words

Korean mistletoe epi-Oleanolic acid Antitumor activity Apoptosis 

References

  1. Akhtar, N. and Malik, A., Oleanane type triterpenes from Plumeria ruba.Phytochemistry, 32, 1523–1525 (1993).CrossRefGoogle Scholar
  2. Budzikiewicz, H., Wilson, J. M., and Djerassi, C., Mass spectrometry in structural and stereochemical problems. XX. Pentacyclic triterpenes.J. Am. Chem. Soc., 25, 3688–3699 (1963).CrossRefGoogle Scholar
  3. Cainelli, G. and Cardillo, G., Chromium oxidations in organic chemistry. Spring-Velag, Berlin Heidelberg, 173 (1984).Google Scholar
  4. Chem, T. K., Ales, D. C., Baenziger, N. C., and Wiemer, D. F., Anti-repellent triterpenoids from Cordia alliodora.J. Org. Chem. 48, 3525–3231 (1983).CrossRefGoogle Scholar
  5. Franz, H., Mistletoe lectins and their A & B chains.Oncology, 43: suppl. 1, 23–28 (1986).PubMedGoogle Scholar
  6. Hajto, T., Hostanska, K., Frei, K., Rordorf, C., and Gabius, H. J., Increased secretion of tumour necrosis factor-α, interleukin 1, and interleukin 6 by human mononuclearcells exposed to β-galactoside lectin from clinically applied mistletoe extract.Cancer Res., 50, 3322–3326 (1990).PubMedGoogle Scholar
  7. Huneck, S., Die Triterpenes uren des Balsams von Liquidambar Orientalis Miller.Tetrahedron, 19, 479–482 (1953).CrossRefGoogle Scholar
  8. Hylands, P. J., Mansour, E. S., and Oskoui, M. T., Bryocoumaric acid, a new triterpene from Bryonia dioica.J. Chem. Soc., Perkin Trans. I, 2933–2936 (1980).CrossRefGoogle Scholar
  9. Jordan, E. and Wagner, H., Structure and properties of polysaccharides fromViscum album (L.),Oncology, 43(Suppl.1), 16–22 (1986)PubMedGoogle Scholar
  10. Khwaja, T. A., Dias, C. B., and Pentecoste, S., Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids.Oncology, 43(Suppl. 1), 42–50 (1986).PubMedCrossRefGoogle Scholar
  11. Khwaja, T. A., Varven, J. C., Pentecost, S., and Pande, H., Isolation of biologically active alkaloids from Korean mistletoe Viscum album, coloratum.Experimenta, 36, 599–600 (1980).CrossRefGoogle Scholar
  12. Kuttan, G., Vasudevan, D. M., and Kuttan, R., Effect of a preparation fromViscum album an on tumor developmentin vitro and in mice.J. Ethnopharmacology, 29, 35–41 (1990).CrossRefGoogle Scholar
  13. Kwon, H. C., Lee, K. R., and Zee, O. P., Cytotoxic constituents of Pilea mongolica.Arch. Pharm. Res., 20, 180–183 (1997).CrossRefPubMedGoogle Scholar
  14. Mahato, S. B. and Kundu, A. P.,13C-NMR spectra of pentacyclic triterpenoids-A compilation and some salient features.Phytochemistry, 37, 1517–1575 (1994).CrossRefGoogle Scholar
  15. Park, J. H., Hyun, C. K., and Shin, H. K., Cytotoxic effects of the compounds in heat-treated mistletoe (Viscum album).Cancer Lett., 139, 207–213 (1999)PubMedCrossRefGoogle Scholar
  16. Seo, S., Tomita, Y., and Tori, K., Carbon-13 NMR spectra of urs-12-enes and application to structural assignments of components ofIsodon japonicus Hara tissue cultures.Tetrahedron Lett., 7–10 (1975).Google Scholar
  17. Schrader, G. and Apel, K., Isolation and characterization of cDNAs encoding viscotoxins of mistletoe (Viscum album).Eur. J. Biochem., 198, 549–553 (1991).PubMedCrossRefGoogle Scholar
  18. Yagi, A., Okamura, N., Haraguchi, Y., Noda, K., and Nishioka, I., Studies on the constituents of Zizyphi Fructus. II. Structure of newp-coumaroylates of maslinic acid.Chem. Pharm. Bull., 26, 3075–3079 (1978).Google Scholar
  19. Yoo, Y. C., Watanabe, R., Koike, Y., Mitobe, M., Shimazaki, K., Watanabe, S., and Azuma, I., Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk-derived peptide: involvement of reactive oxygen species.Biochem. Biophys. Res. Commun., 237, 624–628 (1997).PubMedCrossRefGoogle Scholar
  20. Yoon, T. J., Yoo, Y. C., Choi, O. B., Do, M. S., Kang, T. B., Lee, S. W., Azuma, I., and Kim, J. B., Inhibitory effect of Korean mistletoe (Viscum album coloratum) extract on tumor angiogenesis and metastasis of haematogenous and nonhaematogenous tumour cells in mice.Cancer Lett., 97, 83–91 (1995).PubMedCrossRefGoogle Scholar
  21. Yoon, T. J., Yoo, Y. C., Kang, T. B., Baek, Y. J., Huh, C. S., Song, S. K., Lee, K. H., Azuma, I., and Kim, J. B., Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity.Int. J. Immunopharmacol., 20, 163–172 (1998).PubMedCrossRefGoogle Scholar
  22. Yoon, T. J., Yoo, Y. C., Kang, T. B., Shimazaki, K., Song, S. K., Lee, K. H., Kim, S. H., Park, C. H., Azuma, I., and Azuma, I., Lectins isolated from Korean mistletoe (Viscum album coloratum) induce apoptosis in tumor cells.Cancer Lett., 136, 33–40 (1999).PubMedCrossRefGoogle Scholar
  23. Yoon, T. J., Yoo, Y. C., Kang, T. B., Her, E., Kim, S. H., Kim, K., Azuma, I., and Kim, J. B., Cellular and humoral adjuvant activity of lectins isolated from Korean mistletoe (Viscum album coloratum).Int. Immunopharmacol., 1, 881–889 (2001).PubMedCrossRefGoogle Scholar
  24. Yoon, T. J., Yoo, Y. C., Kang, T. B., Song, S. K., Lee, K. B., Her, E., Song, K. S., and Kim, J. B., Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells.Arch. Pharm. Res., 26, 861–867 (2003).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2004

Authors and Affiliations

  • Myung Ju Jung
    • 1
  • Yung Choon Yoo
    • 2
  • Kyung Bok Lee
    • 3
  • Jong Bae Kim
    • 4
  • Kyung Sik Song
    • 1
    Email author
  1. 1.Division of Applied Biology and Chemistry, College of Agriculture and Life SciencesKyungpook National UniversityDaeguKorea
  2. 2.Department of Microbiology, School of MedicineKonyang UniversityNonsanKorea
  3. 3.Department of Biochemistry, School of MedicineKonyang UniversityNonsanKorea
  4. 4.Department of Biotechnology and Food ScienceHan Dong UniversityPohangKorea

Personalised recommendations