Suppressive effect of Zedoariae rhizoma on pulmonary metastasis of B16 melanoma cells.

The inhibitory effect of Curcuma zedoaria Roscoe (WE-CZ) on experimental pulmonary metastasis of B16 melanoma cells was investigated. The intake of WE-CZ at doses of 250 and 500 mg/kg for 6 weeks from 2 weeks before tumor inoculation significantly reduced the number of metastatic surface nodules in the lung, resulting in an extended life span. When the duration of WE-CZ intake was examined, survival time was not affected by pre-intake before B16 melanoma cell inoculation and was slightly extended by post-intake after B16 melanoma cell inoculation, although the life span was prolonged by intake throughout the experiment. To address the mechanism underlying the anti-metastatic effect of WE-CZ, we examined the issue of whether WE-CZ modulated macrophage function, which is involved in killing tumor cells. The intake of WE-CZ for 6 weeks increased nitric oxide (NO) production by macrophages following stimulation with lipopolysaccharide in a dose-dependent manner. The elevated NO was found to serve as a cytotoxic mediator against B16 melanoma cells in co-culture with macrophages. On the contrary, B16 melanoma-conditioned medium reduced NO production by macrophages. However, WE-CZ treatment significantly reversed the reduction in NO production by the conditioned medium. These findings indicate that WE-CZ possesses anti-migratory effects on B16 melanoma cells and that the macrophage function-modulating activity by WE-CZ appears to underlie its anti-metastatic activity, which leads to a decrease in the number of lung metastatic surface nodules and the extension of life span. These results suggest that WE-CZ may play important roles in the inhibition of cancer metastasis.

Inhibitory effect of methanol extract of Euonymus alatus on matrix metalloproteinase-9.

Various extracts prepared from stems of Euonymus alatus were tested for cytotoxic activity on human hepatocellular carcinoma cell line, Hep3B cells using the XTT assay method. Also, the extracts were investigated the inhibitory effects on matrix metalloproteinase (MMP)-9 activity using gelatin zymography. The methanol extract, hexane and ethyl acetate fraction exhibited weak cytotoxic activity (IC(50) of >100 microg/ml). However, butanol (IC(50)=65 microg/ml) and chloroform (IC(50)=85 microg/ml) fraction exhibited strongly cytotoxic activity. Gelatin zymography showed that the Hep3B cells secreted matrix metalloproteinase (MMP), probably including MMP-9, which may be involved in tumor cell invasion and metastasis. The butanol fraction showed stronger inhibitory effect of proteolytic activity than other fractions. Also, the butanol fraction was able to decrease the proteolytic activity of MMP-9 in a concentration-dependent manner on zymography. These results suggest that the butanol fraction from E. alatus has highly inhibitory effect on MMP-9 in comparatively low cytotoxicity.