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

Abstract

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.