A new anti-metastatic drug, ND-2001, inhibits lung metastases in rat hepatoma cells by suppressing haptotaxis of tumor cells toward laminin.

Abstract

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.

• Authors: Y Kuramitsu, J Hamada, T Tsuruoka, K Morikawa, H Kobayashi, M Hosokawa
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 9 Issue 1 Pg. 88-92 (Jan 1998) ISSN: 0959-4973 [Print] England
• PMID: 9491797 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Laminin
• D-glucaro-delta-lactam
• Glucaric Acid

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Chemotaxis (drug effects)
• Female
• Glucaric Acid (analogs & derivatives, pharmacology)
• Laminin (metabolism)
• Liver Neoplasms, Experimental (pathology)
• Lung Neoplasms (prevention & control, secondary)
• Neoplasm Metastasis
• Rats
• Rats, Wistar
• Tumor Cells, Cultured (drug effects)