Acetyl-L-carnitine is an anti-angiogenic agent targeting the VEGFR2 and CXCR4 pathways

Denisa Baci, Antonino Bruno, Barbara Bassani, Matilde Tramacere, Lorenzo Mortara, Adriana Albini, Douglas M. Noonan

Research output: Contribution to journalArticle

Abstract

Carnitines play an important role in the energy exchange in cells, and are involved in the transport of fatty acids across the inner mitochondrial membrane. L-Acetylcarnitine (ALCAR) is an acetic acid ester of carnitine that has higher bioavailability and is considered a fat-burning energizer supplement. We previously found that in serum samples from prostate cancer (PCa) patients, 3 carnitine family members were significantly decreased, suggesting a potential protective role of carnitine against PCa. Several studies support beneficial effects of carnitines on cancer, no study has investigated the activities of carnitine on tumor angiogenesis. We examined whether ALCAR acts as an “angiopreventive” compound and studied the molecular mechanisms involved. We found that ALCAR was able to limit inflammatory angiogenesis by reducing stimulated endothelial cell and macrophage infiltration in vitro and in vivo. Molecularly, we show that ALCAR downregulates VEGF, VEGFR2, CXCL12, CXCR4 and FAK pathways. ALCAR blocked the activation of NF-κB and ICAM-1 and reduced the adhesion of a monocyte cell line to endothelial cells. This is the first study showing that ALCAR has anti-angiogenic and anti-inflammatory properties and might be an attractive candidate for cancer angioprevention.

Original languageEnglish
Pages (from-to)100-116
Number of pages17
JournalCancer Letters
Volume429
DOIs
Publication statusPublished - Aug 10 2018

Keywords

  • Angiogenesis
  • Angioprevention
  • Chemoprevention
  • L-acetyl-carnitine (ALCAR)
  • Migration/invasion
  • VEGF/VEGFR2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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