We examined the effects of ex vivo treatment of tumor cells with sodium D-glucaro-delta-lactam (sodium 5-amino-5-deoxy-D-glucosaccharic acid-delta-lactam; ND-2001). The ex vivo treatment of rat hepatoma cKDH-8/11 cells with this new synthetic product of the antibiotic nojirimycin, ND-2001 (50 microg/ml), inhibited the experimentally induced lung metastases of the tumor cells significantly at an inhibition rate of 69.2% (one of 10 animals remained metastasis free). Also, it was elucidated in in vitro tumor cell invasion assays that ND-2001 (50 microg/ml) suppressed the invasion activities of cKDH-8/11 cells to Matrigel Matrix at an inhibition rate of 69.3%. However, phagokinetic track assays revealed that ND-2001 did not suppress the random motility of cKDH-8/11 cells. However, ND-2001 (50 microg/ml) suppressed the haptotaxis, another important role in tumor invasion, of cKDH-8/11 cells toward laminin (inhibition rate of 77.0%). These results suggest that ND-2001 suppressed the haptotaxis of tumor cells toward laminin directly at the step of invading the basement membrane and brought about the inhibition of lung metastases.
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Kuramitsu et al. (1998) studied this question.