Open AccessAnti‐angiogenic effect of quercetin and its 8‐methyl pentamethyl ether derivative in human microvascular endothelial cells
Author(s) -
Lupo Gabriella,
Cambria Maria Teresa,
Olivieri Melania,
Rocco Concetta,
Caporarello Nunzia,
Longo Anna,
Zanghì Guido,
Salmeri Mario,
Foti Mario C.,
Anfuso Carmelina Daniela
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14455
Subject(s) - angiogenesis , endothelial stem cell , tyrosine kinase , kinase insert domain receptor , protein kinase b , kinase , cancer research , microbiology and biotechnology , vascular endothelial growth factor , extracellular , ex vivo , chemistry , receptor tyrosine kinase , vascular endothelial growth factor a , biology , pharmacology , signal transduction , in vitro , biochemistry , vegf receptors
Angiogenesis is involved in many pathological states such as progression of tumours, retinopathy of prematurity and diabetic retinopathy. The latter is a more complex diabetic complication in which neurodegeneration plays a significant role and a leading cause of blindness. The vascular endothelial growth factor (VEGF) is a powerful pro‐angiogenic factor that acts through three tyrosine kinase receptors (VEGFR‐1, VEGFR‐2 and VEGFR‐3). In this work we studied the anti‐angiogenic effect of quercetin (Q) and some of its derivates in human microvascular endothelial cells, as a blood retinal barrier model, after stimulation with VEGF‐A. We found that a permethylated form of Q, namely 8MQPM, more than the simple Q, is a potent inhibitor of angiogenesis both in vitro and ex vivo. Our results showed that these compounds inhibited cell viability and migration and disrupted the formation of microvessels in rabbit aortic ring. The addition of Q and more significantly 8MQPM caused recoveries or completely re‐establish the transendothelial electrical resistance (TEER) to the control values and suppressed the activation of VEGFR2 downstream signalling molecules such as AKT, extracellular signal‐regulated kinase, and c‐Jun N‐terminal kinase. Taken together, these data suggest that 8MQPM might have an important role in the contrast of angiogenesis‐related diseases.