Inhibitory effect of agmatine on proliferation of tumor cells by modula-tion of polyamine metabolism

摘要

Aim: To assess the inhibitory effect of agmatine on tumor growth in vivo and tumor cell proliferation in vitro. Methods: The transplanted animal model, [~3H]thymidine incorporation assay, 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazo-lium assay, and lactate dehydrogenase (LDH) release assay were performed. Results: Agmatine, at doses of 5-40 mg/kg, suppressed the S_(180) sarcoma tumor growth dose-dependently in mice in vivo and the highest inhibitory ratio reached 31.3% in Kunming mice and 50.0% in Balb/c mice, respectively. Similar results were obtained in the transplanted B_(16) melanoma tumor model. Agmatine (1-1000 (μmol/L) was able to attenuate the proliferation of cultured MCF-7 human breast cancer cells in vitro in a concentration-dependent manner and the highest inhibitory ratio reached 50.3% in the [~3H]thymidine incorporation assay. Additionally, in the LDH release assay, spermine (20 μamol/L) and spermidine (20 μmol/L) increased the LDH release significantly, but agmatine (1-1000 μmol/ L) did not, indicating that the inhibitory effect of agmatine on the proliferation of MCF was not related to cellular toxicity. In the [~3H]thymidine incorporation assay, putrescine (12.5-100.0 μomol/L) could reverse the inhibitory effect of agmatine on the proliferation of MCF concentration-dependently, suggesting that the inhibitory effect of agmatine on the proliferation of MCF might be associated with a decreased level of the intracellular polyamines pool. Conclusion: Agmatine had significant inhibitory effect on transplanted tumor growth in vivo and proliferation of tumor cells in vitro, and the mechanism might be a result of inducing decrease of intracellular polyamine contents.