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Cancer Lett. 2010 Jan 28;287(2):157-64. doi: 10.1016/j.canlet.2009.06.005. Epub 2009 Jul 1.

Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43).

Author information

1
Center for Medicinal Protein Network and Systems Biology, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.

Abstract

Although AIMP1 was identified as a component of the macromolecular aminoacyl tRNA synthetase complex involved in the cellular translation process, it was also found to be secreted as a cytokine having complex physiological functions. Among these, AIMP1's angiostatic and immune stimulating activities suggest its potential use as a novel antitumor therapeutic protein. Here we evaluated its antitumor efficacy in a mouse xenograft model bearing human stomach cancer cells. Intravenous injection of recombinant AIMP1 for 6 days resulted in significant decreases in both tumor volume and weight. Tumor volume decreased 31.1% and 54.0% when treated with AIMP1 at a concentration of 2mg/kg and 10mg/kg, respectively. Tumor weight decreased 29.1% and 52.2% when treated with AIMP1 at a concentration of 2mg/kg and 10mg/kg, respectively. Proliferating cell nuclear antigen (PCNA) staining of tumor tissues from AIMP1-treated mice (at both 2mg/kg and 10mg/kg) showed a 53% reduction of cells exhibiting an active cell cycle progression. Blood levels of tumor-suppressing cytokines such as TNF-alpha and IL-1beta increased in AIMP1-treated mice, whereas IL-12p40 and IFN-gamma levels remained unaltered. Thus, this work suggests that AIMP1 may exert its antitumor activity by inducing tumor-suppressing cytokines. In a pharmacokinetic study in rats after a single intravenous injection, AMP1 exhibited a low clearance showing a one-compartmental disposition. However, due to a low volume of distribution, AIMP1 had a short half-life of 0.1h. In a serum stability test, AIMP1 showed a half life of >60 min in human serum, 52 min in dog serum and 32 min in rat serum.

PMID:
19573982
DOI:
10.1016/j.canlet.2009.06.005
[Indexed for MEDLINE]

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