Anti-tumor metastatic activity of beta-glucan purified from mutated Saccharomyces cerevisiae.
The beta-glucans isolated from Saccharomyces cerevisiae (S. cerevisiae) enhance the innate immune system, but there is little evidence for its antitumor activity. To examine the antitumor and immunostimulating activities of beta-glucan (IS-2) purified from mutated S. cerevisiae, we made an experiment on innate immune response against metastasis of cancer cells by comparing with the beta-glucan from wild-type S. cerevisiae. In experimental lung metastasis of colon 26-M3.1 carcinoma or B16-BL6 melanoma cells, prophylactic administration of beta-glucan purified from mutated S. cerevisiae significantly inhibited lung metastasis in a dose-dependent manner. Furthermore, therapeutic administration of IS-2 also significantly inhibited the colon 26-M3.1 cell growth in mice. In an assay of liver and spleen metastasis produced by i.v. inoculation of L5178Y-ML25 lymphoma cells, IS-2 also significantly inhibited metastasis in CDF1 mice. Furthermore, pretreatment with IS-2 two days before tumor inoculation significantly prolonged the survival time of tumor-bearing mice. In an in vitro cytotoxicity analysis, IS-2 (up to 100 microg/ml) did not affect the growth of colon 26-M3.1 cells. In contrast, IS-2 enhanced splenocyte proliferating activity in a dose-dependent manner. Peritoneal macrophages stimulated with IS-2 produced various cytokines, such as IL-1beta, IFN-gamma, and IL-12. In addition, treatment with IS-2 (20 microg/mouse) induced tumoricidal activity of peritoneal macrophages against colon 26-M3.1 cells. In an assay for natural killer (NK) cell activity, IS-2 (20 microg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells at 2 days after IS-2 treatment. The depletion of NK cells by injection of rabbit anti-asialo GM1 serum abolished the inhibitory effect of IS-2 on lung metastasis of colon 26-M3.1 cells. These data suggest that IS-2 inhibits tumor metastasis via activation of macrophages and NK cells.
Yoon
Taek Joon
TJ
Bio-Food and Drug Research Center and Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Republic of Korea.
Kim
Tack Joong
TJ
Lee
Hwa
H
Shin
Kwang Soon
KS
Yun
Yeo Pyo
YP
Moon
Won Kook
WK
Kim
Dong Woo
DW
Lee
Kwang Ho
KH
D000818:Animals; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D007940:Leukemia L5178 / Q000628:therapy; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D047071:beta-Glucans / Q000302:isolation & purification* / Q000627:therapeutic use*
D047071:beta-Glucans