Selective tumoricidal effect of soluble proteoglucan extracted from the basidiomycete, Agaricus blazei Murill, mediated via natural killer cell activation and apoptosis |
| |
Authors: | Yoshiaki Fujimiya Youichi Suzuki Ko-ichi Oshiman Hidekazu Kobori Koichi Moriguchi Hisako Nakashima Yonezo Matumoto Shogo Takahara Takusaburo Ebina Ryuichi Katakura |
| |
Institution: | (1) Division of Immunology, Miyagi Cancer Center Research Institute, Natori, Japan 9811293, JP;(2) Division of Neurosurgery, Miyagi Cancer Center Research Institute, Natori, Japan 9811293, JP;(3) Division of Biotechnology, Sumitomo Forestry Tsukuba Research Institute, Tsukuba, Ibaraki, Japan 3002646, JP;(4) Division of Scientific Instrument, Sumika Chemical Analysis Service, Inc., Osaka, Japan 5540022, JP |
| |
Abstract: | We have isolated a novel type of natural tumoricidal product from the basidiomycete strain, Agaricus blazei Murill. Using the double-grafted tumor system in Balb/c mice, treatment of the primary tumor with an acid-treated fraction
(ATF) obtained from the fruit bodies resulted in infiltration of the distant tumor by natural killer (NK) cells with marked
tumoricidal activity. As shown by electrophoresis and DNA fragmentation assay, the ATF also directly inhibited tumor cell
growth in vitro by inducing apoptotic processing; this apoptotic effect was also demonstrated by increased expression of the
Apo2.7 antigen on the mitochondrial membranes of tumor cells, as shown by flow-cytometric analysis. The ATF had no effect
on normal mouse splenic or interleukin-2-treated splenic mononuclear cells, indicating that it is selectively cytotoxic for
the tumor cells. Cell-cycle analysis demonstrated that ATF induced the loss of S phase in MethA tumor cells, but did not affect
normal splenic mononuclear cells, which were mainly in the G0G1 phase. Various chromatofocussing purification steps and NMR
analysis showed the tumoricidal activity to be chiefly present in fractions containing (1→4)-α-D-glucan and (1→6)-β-D-glucan, present in a ratio of approximately 1:2 in the ATF (molecular mass 170 kDa), while the final purified fraction, HM3-G
(molecular mass 380 kDa), with the highest tumoricidal activity, consisted of more than 90% glucose, the main component being
(1→4)-α-D-glucan with (1→6)-β branching, in the ratio of approximately 4:1.
Received: 27 August 1997 / Accepted 22 December 1997 |
| |
Keywords: | Agaricus Natural killer cells α -Glucan Apoptosis |
本文献已被 SpringerLink 等数据库收录! |
|