Skip to main content
Log in

Enhancement of nk cytotoxicity, antimetastasis and elongation effect of survival time in b16-f10 melanoma cells by oregonin

  • Research Articles
  • Articles
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified fromAlnus hirsuta Turcz, Betulaceae. Oregonin is a potential novel immunomodulator, which augments the activation of natural killer (NK) cells, and thereby leads to a powerful antitumor activity. To evaluate the cytotoxicity of oregonin against tumor cells, we examined the effectiveness of NK cells and determined that oregonin could increase NK cell cytotoxicity. This was confirmed by MTT assay. In addition, the survival time of C57BL/6 mice were measured by inoculating B16-F10 melanoma cells to mice via intra muscular (i.m.) injection. Oregonin treatment after 10 hours of inoculation at 10 mg/kg dosage showed a significant extension of survival time by up to 51.32%, when compared to the control group. Moreover, oregonin significantly reduced the incidence of pulmonary metastasis, which may be developed from B16-F10 melanoma cells. These findings suggest that oregonin may be classified as a new and novel immunomodulator due to its potential antitumor activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Al-Rubeai, M., Musgrave, S. G., Lambe, C. A., Walker, A. G., Evans, N. H., and Spier, R. E., Methods for the estimation of the number and quality of animal cells immobilized in carbohydrate gels.Enzyme and Microbial Technology, 12, 459–463 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Anand, A., Pallitaxel in doxorubicin-resistant metastatic breast cancer patients.J. Natl. Cancer. Inst. 87, 21, 1642 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Biron, C. A., Su, H.C., Orange, J.S., Orange, Function, and Regulation of Natural Killer (NK) Cells during Viral Infections: Characterization of Responsesin vivo.A Companion to Methods in Enzymology 9, 2, 379–393 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Chihara, G., Hamuro, H., Maeda, Y., Arai, Y., and Fukuoka, K., Fractionation and purification of the polysaccharides with marked antitumor activity, especially lentinan fromLentinus edodes.Cancer Res., 30, 2776–2781 (1970).

    PubMed  CAS  Google Scholar 

  • Doug, H., Chen, S. X., Xu, H. X., Kadota, S., Namba, T., A new antiplatelet diarylheptanoid from Alpinia blepharocalyx.J. Nat. Prod., 61, 1, 142–4 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Fidler I. J., Selection of successive tumor lines for metastasis.Nature (New Biol) 242, 148–149, (1973).

    CAS  Google Scholar 

  • Fritzer-Szekeres, M., Novotny, L., Romanova, D., Gobl, R., Sedlak, J., Vachalkova, A., Rauko, P., Elford, H.L., Szekeres, T., Enhanced effects of adriamycin by combination with a new ribonucleotide reductase inhibitor, trimidox, in murine leukemia.Life Sci. 63 7, 545–552 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Furukawa, T., Kubota, T., Watanabe, M., Kuo, T.H., Kitajima, M., Hoffman, R.M., Differential chemosensitivity of local and metastatic human gastric cancer after orthotropic transplantation of histologically intact tumor tissue in nude mice.Int. J. Cancer, 54, 397–401 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Gallagher G., Rees R. C., Reynolds C. W., Tumor Immunobiology. A Practical Approach, 121, (1992).

  • Halary, F., Peyrat, M. A., Champagne, E., Lopez Botet, M., Moretta, A., Moretta, L., Vi, H., Fourni, J. J., Bonneville, M., Control of self-reactive cytotoxic T lymphocytes expressing gamma delta T cell receptors by natural killer inhibitory receptors.Eur. J. Immunol., 27, 11, 2812–21 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Jurgen Kiefer, Biological Radiation Effect Springer-Verlag Berlin Heidelberg,Germany (1990).

    Google Scholar 

  • Kawai, N., Ando, Y.U., Ando, Y.O., and Nishibe, Y., Extraction of antimutagenic tannins fromAlnus firma plant.Patent-Japan Kokai Tokyo Koho-O2 117, 685 (1990).

    Google Scholar 

  • Killion, J. J., Fidler, J. J., Therapy of cancer metastasis by tumoricidal activation of tissue macrophages using liposomeencapsulated immunomodulators.Pharmacol. Ther.,78, 3, 141–154 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Kiuchi, F.,et al., Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids.Chem. Pharm Bull (Tokyo), 40, 2, 387–91 (1992).

    CAS  Google Scholar 

  • Komatsu, N., Okubo, S., Likumoto, S., Kimura, K., Saito, G., and Sakai, S., Host-mediated antitumor action of schizo-phyllan, a glucan produced bySchizophyllum commune.Gann, 60, 137 (1969).

    PubMed  CAS  Google Scholar 

  • Manoussaka, M., Georgiou, A., Rossiter, B., Shrestha, S., Toomey, J. A., Sivakumar, P. V., Bennett, M., Kumar, V., Brooks, C. G., Phenotypic and functional characterization of long-lived NK cell lines of different maturational status obtained from mouse fetal liver.J. Immunol., 158, 1, 112–9 (1997).

    PubMed  CAS  Google Scholar 

  • Monsmann, T., Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assays.J. Immunol. Meth., 65, 55–63 (1983).

    Article  Google Scholar 

  • Myoungyun, P., Sumi, H. Kisook Y., Effects of Phellinus linteus extracts on the Humoral Immune Response in Normal and Cyclophosphamide-treated Mice.J. Appl. Pharmacol., 9, 194–2000 (2001).

    Google Scholar 

  • Ohishi, K., Morinaga, Y., Ohsumi, K., Nakagawa, R., Suga, Y., Tsuji, T., Akiyama, Y., Tsuruo, T., Potentiation of antitumor and antimetastatic activities of adriamycin by a novelN-alkylated dihydropyridine, AC394, and its enantiomers in colon cancer-bearing mice.Cancer Chemother. Pharmacol. 38 5, 446–452 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Ohno, N., Suzuki, I., Oikawa, S., Sato, K., Miyazaki, T., and Yadomae, T., Antitumor activity and structure characterization of glucans, extracted from cultured fruit bodies ofGrifola frondosa.Chem. Pharm. Bull., 32, 1142–1151 (1984).

    PubMed  CAS  Google Scholar 

  • Poccia, F., Cipriani, B., Vendetti, S., Colizzi, V., Poquet, Y., Battistini, L., Lpez, Botet, M., Fourni J. J., Gougeon, M. L., CD94/NKG2 inhibitory receptor complex modulates both anti-viral and antitumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes.J. Immunol., 159, 12, 6009–17 (1997).

    PubMed  CAS  Google Scholar 

  • Prasain, J. K., Tezuka, Y., Hase, K., Basnet, P., Dong, H., Namba, T., Kadota, S., Inhibitory effect of diarylheptanoids on nitric oxide production in activated murine macrophages.Biol. Pharm. Bull., 21:4, 371–4 (1998).

    PubMed  CAS  Google Scholar 

  • Sangbae, H., Changwoo L., Youngjin J., Namdoo H., Ickdong Y., Kyuhwan Y., Hwanmook K., The inhibitory effect of polysaccharides isolated fromPhenllinus linteus on tumor growth and metastasis.Immunopharmacology 41, 157–164 (1999).

    Article  Google Scholar 

  • Saxena, G., Farmer, S., Hancock, R. E. W., and Towers, G. H. N., Antimicrobial compounds fromAlnus rubra.Int. J. Pharmacog., 33, 33–36 (1995).

    Article  CAS  Google Scholar 

  • Sheth, K., Bianchi, E., Wiedhopf, R. and Cole, J. R., Antitumor agents fromAlnus oregona (Betulaceae).J. Pharm. Sci., 62, 139 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Timonen, T., J. R. Ortaldo, and R. B. Herberman, Characteristics of human large granular lymphocytes and relationship to nature killer and K-cells.J. Exp. Med. 153, 569–582 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki, R., Aiyama, R., Matsuzaki, T., Hashimoto, S., Yokokura, T., Anti-inflammatory effect of YPE-01, a novel diarylheptanoid derivative, on dermal inflammation in mice.Inflamm. Res., 47, 4, 182–6 (1998).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Do-Ik Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Joo, SS., Kim, MS., Oh, WS. et al. Enhancement of nk cytotoxicity, antimetastasis and elongation effect of survival time in b16-f10 melanoma cells by oregonin. Arch Pharm Res 25, 493–499 (2002). https://doi.org/10.1007/BF02976608

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02976608

Key words

Navigation