Carnitines play an important role in the energy exchange in cells, 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 than carnitine 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 act 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 showed 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-angiogenesis and anti-inflammatory properties and might be attractive candidate for cancer angioprevention

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.

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

A. Bruno;B. Bassani;L. Mortara;A. Albini
;
D. M. Noonan
2018

Abstract

Carnitines play an important role in the energy exchange in cells, 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 than carnitine 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 act 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 showed 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-angiogenesis and anti-inflammatory properties and might be attractive candidate for cancer angioprevention
www.elsevier.com/locate/canlet
Angiogenesis; Angioprevention; Chemoprevention; L-acetyl-carnitine (ALCAR); Migration/invasion; VEGF/VEGFR2;
Baci, D.; Bruno, A.; Bassani, B.; Tramacere, M.; Mortara, L.; Albini, A.; Noonan, D. M.
File in questo prodotto:
File Dimensione Formato  
Mortara L.-Cancer Lett-2018.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Documento in Post-print
Licenza: DRM non definito
Dimensione 9.97 MB
Formato Adobe PDF
9.97 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2072296
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 16
social impact