We previously found that
ergosterol isolated from Agaricus blazei inhibited
tumor growth through the inhibition of
tumor-induced neovascularization. In the present study, we isolated further anti-angiogenic substances (A-1 and A-2) from this fungus using an assay system of angiogenesis induced by
Matrigel supplemented with
vascular endothelial growth factor, and A-1 was identified as
sodium pyroglutamate. Next, we examined the antitumor and antimetastatic actions of A-1 using
Lewis lung carcinoma (LLC)-bearing mice. A-1 (30, 100 and 300 mg/kg) inhibited
tumor growth and
metastasis to the lung. The reduction of the numbers of splenic lymphocytes, CD4+ and CD8+ T cells in LLC-bearing mice was inhibited by the
oral administration of A-1 (30, 100 and 300 mg/kg). Further, A-1 increased the number of apoptotic cells of
tumors and the numbers of CD8+ T and natural killer cells invading the
tumors, and inhibited the increase of
von Willebrand factor expression (a measure of angiogenesis) in the
tumors. These results suggest that the antitumor and antimetastatic actions of A-1 (
sodium pyroglutamate) may be associated with inhibition of the reduction of immune response caused by the
tumor growth and
tumor-induced neovascularization. This is the first report showing that
sodium pyroglutamate isolated from A. blazei as an anti-angiogenic substance has potent antitumor and antimetastatic actions, as well as immune-modulatory activity, in
tumor-bearing mice.