Enhancement of NK Cytotoxicity, Antimetastasis and Elongation Effect of Survival Time in B16-F10 Melanoma Cells by Oregonin

  • Joo, Seong-Soo (Division of Immunology, College of Pharmacy, Chungang University) ;
  • Kim, Min-Soo (Division of Immunology, College of Pharmacy, Chungang University) ;
  • Oh, Won-Sik (Division of Immunology, College of Pharmacy, Chungang University) ;
  • Lee, Do-Ik (Division of Immunology, College of Pharmacy, Chungang University)
  • Published : 2002.08.01

Abstract

We investigated the antitumor activity of oregonin, a diarylheptanoid derivative purified from Alnus 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 816-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 816-F10 melanoma cells. These findings suggest that oregon in may be classified as a new and novel immunomodulator due to its potential antitumor activity.

Keywords

References

  1. AI-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) https://doi.org/10.1016/0141-0229(90)90058-X
  2. Anand, A., Pallitaxel in doxorubicin-resistant metastatic breast cancer patients. J. Natl. Cancer. Inst. 87 21, 1642 (1995)
  3. Biron, C. A., Su, H.C., Orange, J. S., Orange, Function, and Regulation of Natural Killer (NK) Cells during Viral Infections: Characterization of Responses in vivo. A Companion to Methods in Enzymology, 9, 2, 379-393 (1996) https://doi.org/10.1006/meth.1996.0043
  4. Chihara, G., Hamuro, H., Maeda, Y., Arai, Y., and Fukuoka, K., Fractionation and purification of the polysaccharides with marked antitumor activity, especially lentinan from Lentinus edodes. Cancer Res., 30, 2776-2781 (1970)
  5. 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) https://doi.org/10.1021/np970293i
  6. Fidler I. J., Selection of successive tumor lines for metastasis. Nature (New Biol)242, 148-149, (1973) https://doi.org/10.1038/newbio242148a0
  7. Fritzer-Szekeres, M., Novotny, L., Romanova, D., Gobi, 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) https://doi.org/10.1016/S0024-3205(98)00305-1
  8. 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. lnt. J. Cancer, 54, 397-401 (1993) https://doi.org/10.1002/ijc.2910540308
  9. Gallagher G., Rees R. C., Reynolds C. W., Tumor Immunobiology. A Practical Approach, 121, (1992)
  10. 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. lmmunol., 27, 11, 2812-21 (1997) https://doi.org/10.1002/eji.1830271111
  11. Jurgen Kiefer, Biological Radiation Effect Springer-Verlag Berlin Heidelberg, Germany, (1990)
  12. Kawai, N., Ando, Y.U., Ando, Y.O., and Nishibe, Y., Extraction of antimutagenic tannins from Alnus firma plant. Patent-Japan Kokai Tokyo Koho-O2 117, 685 (1990)
  13. 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) https://doi.org/10.1016/S0163-7258(98)00004-7
  14. Kiuchi, F., et al., Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. Chem. Pharm Bull (Tokyo), 40, 2, 387-91 (1992) https://doi.org/10.1248/cpb.40.387
  15. Komatsu, N., Okubo, S., Likumoto, S., Kimura, K., Saito, G., and Sakai, S., Host-mediated antitumor action of schizophyllan, a glucan produced by Schizophyllum commune. Gann, 60, 137 (1969)
  16. 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)
  17. Monsmann, T., Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxicity assays. J. Immunol. Meth., 65, 55-63 (1983) https://doi.org/10.1016/0022-1759(83)90303-4
  18. Myoungyun, P., Sumi, H. Kisook Y., Effects of Phellinus Iinteus extracts on the Humoral Immune Response in Normal and Cyclophosphamide-treated Mice. J. Appl. Pharmacol., 9, 194-2000 (2001)
  19. 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 novel Nalkylated dihydropyridine, AC394, and its enantiomers in colon cancer-bearing mice. Cancer Chemother. Pharmacol. 385, 446-452 (1996)
  20. 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 of Grifola frondosa. Chem. Pharm. Bull., 32, 1142-1151 (1984) https://doi.org/10.1248/cpb.32.1142
  21. Poccia, F., Cipriani, B., Vendetti, S., Calizzi, V., Paquet, 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)
  22. 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) https://doi.org/10.1248/bpb.21.371
  23. Sangbae, H., Changwoo L., Youngjin J., Namdoo H., Ickdong Y., Kyuhwan Y., Hwanmook K., The inhibitory effect of polysaccharides isolated from Phenllinus Iinteus on tumor growth and metastasis. Immunopharmacology, 41, 157-164(1999) https://doi.org/10.1016/S0162-3109(98)00063-0
  24. Saxena, G., Farmer, S., Hancock, R. E. W., and Towers, G.H.N. Antimicrobial compounds from Alnus rubra. Int. J. Phanrmecog., 33, 33-36 (1995) https://doi.org/10.3109/13880209509088144
  25. Shetn K., Bianchi, E., Wiedhopf, R. and Cole, J. R., Antitumor agents from Alnus oregona (Betulaceae). J. Pharm. Sci., 62, 139 (1973) https://doi.org/10.1002/jps.2600620129
  26. Timorenm, 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) https://doi.org/10.1084/jem.153.3.569
  27. 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) https://doi.org/10.1007/s000110050315