Reticulol was isolated from the culture broth of the strain Streptoverticillium sp. NA-4803. Recticulol (M.W. 222.2) exhibited a potent in vitro cytotoxicity against A427, a human lung tumor cell line, and B16F10, a mouse
melanoma cell line. In the
trypan blue staining assay for B16F10 cells, the cell viability by
reticulol treatment was significantly decreased in a dose-dependent manner. The in vivo assay for the lung
metastasis-blocking effect showed that
reticulol injected intravenously suppressed the increase in colonies on the lung in a dose-dependent manner. In addition, the survival rate of
tumor-implanted mice treated with
reticulol was closely associated with its antitumoral efficacy.
Reticulol administered via the peritoneum of mice showed less
metastasis inhibition than that injected intravenously. To demonstrate the mechanism for inhibition of
metastasis, the inhibitory effect of
reticulol for
matrix metalloproteinase-2 or -9 involved in
melanoma metastasis was investigated; however, they were not observed on zymogram gel. In addition, the antitumor efficacy of
reticulol was not associated with cell cycle arrest or apoptosis. Therefore, it was inferred that
reticulol known as a
phosphodiesterase inhibitor directly inhibited the growth of B16F10
melanoma, showing necrotic response. These results suggest that
reticulol protects its lung
metastasis via the bloodstream by inhibiting the growth of B16F10
melanoma at the cellular level.