Inhibitory effect of agmatine on proliferation of tumor cells by modulation of polyamine metabolism.
OBJECTIVE
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 micromol/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 micromol/L) and spermidine (20 micromol/L) increased the LDH release significantly, but agmatine (1-1000 micromol/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 micromol/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.


CONCLUSIONS
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.
Wang
Ji-fang
JF
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Su
Rui-bin
RB
Wu
Ning
N
Xu
Bo
B
Lu
Xin-qiang
XQ
Liu
Yin
Y
Li
Jin
J
D000376:Agmatine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D012510:Sarcoma 180 / Q000473:pathology*
D011073:Polyamines; D000376:Agmatine; D007770:L-Lactate Dehydrogenase; D011700:Putrescine