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Glutamine inhibits platelet-activating factor-mediated pulmonary tumour metastasis.

Abstract
Inflammation has been increasingly recognised as an important component of tumourigenesis. Platelet-activating factor (PAF), a potent inflammatory mediator, has the ability to enhance tumour growth and metastasis. In this study, we have investigated (i) the role of mitogen-activated protein kinases (MAPKs) and (ii) the therapeutic efficacy of the non-essential amino acid, l-glutamine (Gln), which evidences MAPKs inhibition activity in PAF-mediated B16F10 melanoma metastasis to the lungs. Mice were given intraperitoneal injection of PAF. ERK, JNK, and p38 MAPKs were activated rapidly by PAF in the lungs, and the PAF-induced metastasis of B16F10 was inhibited in a dose-dependent manner by pretreatment with either U0126 (ERK inhibitor), SP600125 (JNK inhibitor), or SB202190 (p38 inhibitor). Intraperitoneal administration of Gln after, but not before, PAF injection deactivated ERK, JNK, and p38 by dephosphorylating them. Gln inhibited PAF-induced metastasis when Gln was administered either intraperitoneally or orally. PAF induced pronounced angiogenic activity in an in vivo mouse Matrigel implantation model. MAPK inhibitors as well as Gln significantly inhibited PAF-induced angiogenesis. These data indicate that Gln exerts a beneficial effect against inflammation-associated enhanced tumour metastasis via the deactivation of MAPKs.
AuthorsHan-A Kim, Kyoung-Jin Kim, So Young Yoon, Hern-Ku Lee, Suhn-Young Im
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 48 Issue 11 Pg. 1730-8 (Jul 2012) ISSN: 1879-0852 [Electronic] England
PMID21889331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Platelet Activating Factor
  • Glutamine
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Cell Line, Tumor
  • Female
  • Glutamine (pharmacology)
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Lung Neoplasms (prevention & control, secondary)
  • Melanoma, Experimental (pathology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Neovascularization, Pathologic (prevention & control)
  • Platelet Activating Factor (pharmacology)

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