Abstract
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-diphenyltetrazolium assay, and lactate dehydrogenase (LDH) release assay were performed.
Results:
Agmatine, at doses of 5–40 mg/kg, suppressed the S180 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 B16 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 μmol/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 μmol/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.
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Project supported by the Hi-Tech Research Program of China (20002AA2Z3028) and the National Basic Scientific Research and Development Program of China (2003CB515400).
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Wang, Jf., Su, Rb., Wu, N. et al. Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism. Acta Pharmacol Sin 26, 616–622 (2005). https://doi.org/10.1111/j.1745-7254.2005.00084.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00084.x
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