INHIBITORY EFFECT OF A BISCOCLAURINE ALKALOID, CEPHARANTHIN, ON LUNG METASTASIS OF LEWIS LUNG-CARCINOMA

The antimetastatic effect of cepharanthin with or without 5-fluorouracil (5-FU) was examined in an experimental model of lung metastasis induced by Lewis lung carcinoma (3LL) in C57BL/6crSlc mice. Injection of cepharanthin i.p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination therapy with cepharanthin plus 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i.v. injection of peritoneal macrophages activated with cepharanthin. Cepharanthin depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood) was increased significantly by coadministration of cepharanthin. A possible mechanism of the inhibition of lung metastases by treatment with cepharanthin may be that this drug acts through macrophage activation and depression of the hepatic microsomal drug-metabolizing system. These findings raise the possibility that combination therapy with cepharanthin plus 5-FU may have clinical value in the prevention of cancer metastasis.