Effects of D-Fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells.
Natural killer (NK) cells are directly cytotoxic for tumor cells and play a primary role in regulating immune responses. We monitored levels of NK cell cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were maintained for one year. To elucidate the mechanisms underlying long-term activation of NK cells during treatment with D-Fraction, we examined tumor volume and levels of IFN-gamma and TNF-alpha in MM46-bearing C3H/HeN mice to which D-Fraction was administered for 19 d. D-Fraction markedly suppressed tumor growth, corresponding with increases in TNF-alpha and IFN-gamma released from spleen cells and a significant increase in TNF-alpha expressed in NK cells. This suggests that the D-Fraction activates NK cells even on the 20th day after treatment. Furthermore, D-Fraction increased macrophage-derived interleukin (IL)-12, which serves to activate NK cells. These results suggest that NK cells are not only responsible for the early effects of D-Fraction on tumor growth, but also for the long-term tumor-suppressive effects of D-Fraction through increased IL-12 released from macrophages.
Kodama
Noriko
N
Department of Microbial Chemistry, Kobe Pharmaceutical University, Japan. n-kokama@kobepharma-u.ac.jp
Komuta
Kiyoshi
K
Sakai
Norio
N
Nanba
Hiroaki
H
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000328:Adult; D000363:Agaricales / Q000737:chemistry / Q000302:isolation & purification; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000276:Adjuvants, Immunologic; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D018664:Interleukin-12