Antiangiogenic Activity of Xanthomicrol and Calycopterin, Two Polymethoxylated Hydroxyflavones in Both In Vitro and Ex Vivo Models

Abstract

Our previous studies had shown xanthomicrol and calycopterin, two plant-derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 µg/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 µg/mL. Suramin and thalidomide, used at 20 µg/mL as positive controls, inhibited microvessel formation by 23% and 64%, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 µg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 µg/mL, but they had little or no effect on b-FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression.

Evaluation of the cytotoxic effects of Cyperus longus extract, fractions and its essential oil on the PC3 and MCF7 cancer cell lines

“…Several anticancer drugs, such as vincristine, etoposide, vinblastine, irinotecan, paclitaxel (taxol) and topotecan are botanical secondary metabolites or semi-synthetic derivatives ( 1 ). Apigenin ( 2 ), deguelin ( 3 ), kaempferol ( 4 ), luteolin ( 5 – 7 ), quercetin ( 8 – 11 ), rutin ( 12 – 16 ), tricin ( 17 ), xanthomicrol ( 18 ), α-copaene ( 19 ), α-humulene ( 20 , 21 ) and β-himachalene ( 22 ) are some botanical ingedients that have been investigated as possible future remedies for use in chemotherapy. Xanthomicrol and calycopterin have also been shown to exert potent inhibitory effects on microvessel outgrowth and that these anti-angiogenic effects enhance the antitumor activity ( 18 ).…”

Cytotoxic Flavonoids from the Aerial Parts of Stachys lavandulifolia Vahl

“…50 Potent antiangiogenic activity of xanthomicrol and calycopterin from the aerial parts of Dracocephalum kotschi and its relation with inhibition of VEGF (vascular endothelial growth factor) expression has been shown during previous investigations. 51 Beside cytotoxic activity, viscosine has been previously reported for its anxiolytic and anticonvulsant effects via GABAA receptor modulation. 52 Therefore, this major flavonoid isolated from the chloroform extract of S. lavandulifolia, could be considered as an active compound involved in anxiolytic activity of S. lavandulifolia extracts documented by Rabbani et al 10 Some hormone induced effects followed by administration of the aerial parts of S. lavandulifolia may be associated with the presence of penduletin and apigenin, flavonoids with confirmed estrogen receptor-β (ERβ) selective activity.…”

3-Bromopyruvate potentiates TRAIL-induced apoptosis in human colon cancer cells through a reactive oxygen species- and caspase-dependent mitochondrial pathway

“…The medium was then replaced with 150 µl dimethyl sulfoxide (DMSO) per well to solubilize the formazan crystals. Finally, the absorbance was measured at 570 nm using a microplate reader (Biotek, H1M, USA) (Abbaszadeh et al 2014).…”