Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol

被引:77
作者
Hasegawa, H
Suzuki, R
Nagaoka, T
Tezuka, Y
Kadota, S
Saiki, I
机构
[1] Happy World Inc, Itto Inst Life Sci Res, Fuchu, Tokyo 1830011, Japan
[2] Toyama Med & Pharmaceut Univ, Inst Nat Med, Dept Pathogen Biochem, Toyama 9300194, Japan
[3] Toyama Med & Pharmaceut Univ, Dept Nat Prod Chem, Toyama 9300194, Japan
关键词
ginsenoside; 20(S)-protopanaxatriol (M4); fatty acid; esterification; immunostimulation; NK cell;
D O I
10.1248/bpb.25.861
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ginsenosides, the glycosides of Panav ginseng, are metabolized (deglycosylated) by intestinal bacteria after oral administration. 20(S)-Protopanaxatriol (M4) is the main bacterial metabolite of protopanaxatriol-type ginsenosides and mediates their antitumor effects. To clarify the mechanism of the M4-mediated antitumor effect, the antitumor activity and metabolism of M4 was examined, using the C57BL/6 mice implanted with B16-BL6 melanoma. The chronic oral administration of M4 inhibited the growth of B16-BL6 melanoma at the implanted site. Analyses using TLC, HPLC, MS and NMR suggest that orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its accumulation in the tissues including the liver and lung. The administration of M4 prior to the intravenous injection of B16-BL6 cells abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GM1. The esterified M4 (EM4) did not directly affect tumor growth in vitro, whereas it stimulated splenic NK cells to become cytotoxic to tumor cells. These results indicate that the antitumor activity of M4 is based on the NK cell-mediated tumor lysis enhanced by EM4.
引用
收藏
页码:861 / 866
页数:6
相关论文
共 26 条
  • [1] Ahn YO, 1997, INT J CANCER, P7
  • [2] DUC NM, 1994, CHEM PHARM BULL, V42, P634
  • [3] Main Ginseng saponin metabolites formed by intestinal bacteria
    Hasegawa, H
    Sung, JH
    Matsumiya, S
    Uchiyama, M
    [J]. PLANTA MEDICA, 1996, 62 (05) : 453 - 457
  • [4] Hasegawa H., 2000, Journal of Traditional Medicines, V17, P186
  • [5] Hasegawa H., 2001, Journal of Traditional Medicines, V18, P217
  • [6] Hasegawa H, 2000, BIOL PHARM BULL, V23, P298, DOI 10.1248/bpb.23.298
  • [7] Hasegawa Hideo, 2000, Microbial Ecology in Health and Disease, V12, P85, DOI 10.1080/089106000435473
  • [8] CHEMICAL CONSTITUENTS OF GINSENG PLANTS
    HOU, JP
    [J]. COMPARATIVE MEDICINE EAST AND WEST, 1977, 5 (02): : 123 - 145
  • [9] Kasai R, 2000, CHEM PHARM BULL, V48, P1226
  • [10] Kobashi K., 1997, Bioscience and Microflora, V16, P1