Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model.
OBJECTIVE
The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer.


METHODS
We examined whether beta-(1-6)-D: -glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model.


RESULTS
Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies.


CONCLUSIONS
Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.
Kobayashi
Hiroshi
H
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama 1-20-1, Hamamatsu, Shizuoka 431-3192, Japan. hirokoba@hama-med.ac.jp
Yoshida
Ryuji
R
Kanada
Yasufumi
Y
Fukuda
Yoichi
Y
Yagyu
Tatsuo
T
Inagaki
Kiyokazu
K
Kondo
Toshiharu
T
Kurita
Noriyuki
N
Suzuki
Mika
M
Kanayama
Naohiro
N
Terao
Toshihiko
T
D000284:Administration, Oral; D000364:Agaricus; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D047071:beta-Glucans / Q000008:administration & dosage / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D047071:beta-Glucans; C064197:beta-1,6-glucan; D048051:p38 Mitogen-Activated Protein Kinases