@article{APS3719,
author = {Ji-fang Wang and Rui-bin Su and Ning Wu and Bo Xu and Xin-qiang Lu and Yin Liu and Jin Li},
title = {Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism},
journal = {Acta Pharmacologica Sinica},
volume = {26},
number = {5},
year = {2016},
keywords = {},
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 mumol/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 mumol/L) and spermidine (20 mumol/L) increased the LDH release significantly, but agmatine (1–1000 mumol/ 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 mumol/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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3719}
}