Evaluation of antioxidant, antiangiogenic and antitumor properties of Anogeissus leiocarpus against colon cancer

Abstract

Anogeissus leiocarpus is a traditional medicinal plant, used to treat diarrhea, fever, coughs, rheumatism, leprosy, wounds and skin diseases and psoriasis. This study was aimed to investigate the antiangiogenic and cytotoxic effects of six extracts from Anogeissus leiocarpus (leaves and bark). Further, the tested biological activities were correlated with antioxidant capabilities, total phenolic and total flavonoid contents. In order to confirm the effect of the extract on motility of human endothelial cells, cell migration assay was conducted. In addition, VEGF suppressive effect of the extracts was assessed in endothelial cells. Finally, the antitumor effect of the leaves ethanolic extract was evaluated using in vivo human tumor xenograft model. A. leiocarpus extracts significantly inhibited the outgrowth of new vessels from rat aortic tissue explants by more than 50%. Hexane extract of the stem bark and ethanolic leaves extract profoundly inhibited the sprouting of microvessels (by 89.56% and 87.12% respectively) in rat aortic ring assay. The ethanol extract of the leaves inhibited HUVEC migration by 87.57 and 65.23% after 18 hours at 80µg/ml and 40µg/ml concentrations respectively; it also demonstrated significant inhibition of VEGF levels (45.32% and 30.52 % respectively) in treated endothelial cells. The ethanol extract of the leaves showed remarkable DPPH scavenging effect with IC50 = 29.87µg/ml. Furthermore, it displayed higher levels of total phenolics and flavonoids compared to other extracts. Finally the ethanol extract of the leaves exhibited potent anti-tumorigenic effect in anthymic mice with ?T/?C =2.97 and 7.54% at doses 400 and 200mg/kg, respectively. These results may provide novel guidelines towards improved strategies using Anogeissus leiocarpus extracts based on the suppression of angiogenesis to curb tumors growth. The plant can be used as promising candidate for anti-neoplasic drug development.