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

Jung Min Han, Heejoon Myung, Sunghoon Kim

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 2 mg/kg and 10 mg/kg, respectively. Tumor weight decreased 29.1% and 52.2% when treated with AIMP1 at a concentration of 2 mg/kg and 10 mg/kg, respectively. Proliferating cell nuclear antigen (PCNA) staining of tumor tissues from AIMP1-treated mice (at both 2 mg/kg and 10 mg/kg) showed a 53% reduction of cells exhibiting an active cell cycle progression. Blood levels of tumor-suppressing cytokines such as TNF-α and IL-1β increased in AIMP1-treated mice, whereas IL-12p40 and IFN-γ 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 0.1 h. 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. Crown

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalCancer Letters
Volume287
Issue number2
DOIs
Publication statusPublished - 2010 Jan 28

Fingerprint

Tumor Burden
Pharmacokinetics
Cytokines
Serum
Intravenous Injections
Half-Life
Proteins
Interleukin-12 Subunit p40
Amino Acyl-tRNA Synthetases
Neoplasms
Proliferating Cell Nuclear Antigen
Crowns
Interleukin-1
Heterografts
Stomach Neoplasms
Cell Cycle
Dogs
Staining and Labeling
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43)",
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 2 mg/kg and 10 mg/kg, respectively. Tumor weight decreased 29.1{\%} and 52.2{\%} when treated with AIMP1 at a concentration of 2 mg/kg and 10 mg/kg, respectively. Proliferating cell nuclear antigen (PCNA) staining of tumor tissues from AIMP1-treated mice (at both 2 mg/kg and 10 mg/kg) showed a 53{\%} reduction of cells exhibiting an active cell cycle progression. Blood levels of tumor-suppressing cytokines such as TNF-α and IL-1β increased in AIMP1-treated mice, whereas IL-12p40 and IFN-γ 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 0.1 h. 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. Crown",
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Antitumor activity and pharmacokinetic properties of ARS-interacting multi-functional protein 1 (AIMP1/p43). / Han, Jung Min; Myung, Heejoon; Kim, Sunghoon.

In: Cancer Letters, Vol. 287, No. 2, 28.01.2010, p. 157-164.

Research output: Contribution to journalArticle

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