Isolation of an anti-angiogenic substance from Agaricus blazei Murill: Its antitumor and antimetastatic actions

Cancer Science

We previously found that ergosterol isolated from Agaricus blazei inhibited tumor growth through the inhibition of tumor-in-duced neovascularization. In the present study, we isolated fur-ther anti-angiogenic substances (A-1 and A-2) from this fungus using an assay system of angiogenesis induced by Matrigel sup-plemented with vascular endothelial growth factor, and A-1 was identified as sodium pyroglutamate. Next, we examined the anti-tumor and antimetastatic actions of A-1 using Lewis lung carci-noma (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 apop-totic cells of tumors and the numbers of CD8 + T and natural killer cells invading the tumors, and inhibited the increase of von Wille-brand factor expression (a measure of angiogenesis) in the tu-mors. These results suggest that the antitumor and antimetastatic actions of A-1 (sodium pyroglutamate) may be associated with in-hibition of the reduction of immune response caused by the tu-mor 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. (Cancer Sci 2004; 95: 758–764)