Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism.

To assess the inhibitory effect of agmatine on tumor growthin vivoand tumor cell proliferationin vitro.The transplanted animal model, [³H]thymidine incorporation assay, 3-[4, 5-dimethythiazol-2-yl]-2, 5-diphenyltetrazolium assay, and lactate dehydrogenase (LDH) release assay were performed.Agmatine, at doses of 5–40 mg/kg, suppressed the S₁₈₀ sarcoma tumor growth dose-dependently in micein vivoand 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 B16 melanoma tumor model. Agmatine (1–1000μmol/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 (20μmol/L) and spermidine (20μmol/L) increased the LDH release significantly, but agmatine (1–1000μmol/ 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 (12.5–100.0μmol/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.Agmatine had significant inhibitory effect on transplanted tumor growthin vivoand proliferation of tumor cellsin vitro, and the mechanism might be a result of inducing decrease of intracellular polyamine contents. [ABSTRACT FROM AUTHOR]