Abstract
Context: Abnormal angiogenesis and evasion of apoptosis are hallmarks of cancer. Accordingly, anti-angiogenic and pro-apoptotic therapies are effective strategies for cancer treatment. Medicinal plants, namely, Eugenia jambolana Lam. (Myrtaceae), Musa paradisiaca L. (Musaceae), and Coccinia indica Wight & Arn. (Cucurbitaceae), have not been greatly investigated for their anticancer potential.Objective: We investigated the anti-angiogenic and pro-apoptotic efficacy of ethyl acetate (EA) and n-butanol (NB) extracts of E. jambolana (seeds), EA extracts of M. paradisiaca (roots) and C. indica (leaves) with respect to mammary neoplasia.Materials and methods: Effect of extracts (2–200 μg/mL) on cytotoxicity and MCF-7, MDA-MB-231 and endothelial cell (EC) proliferation and in vitro angiogenesis were evaluated by MTT, 3[H]thymidine uptake and EC tube formation assays, respectively. In vivo tumour proliferation, VEGF secretion and angiogenesis were assessed using the Ehrlich ascites tumour (EAT) model followed by rat corneal micro-pocket and chicken chorioallantoic membrane (CAM) assays. Apoptosis induction was assessed by morphological and cell cycle analysis.Results: EA extracts of E. jambolana and M. paradisiaca exhibited the highest cytotoxicity (IC50 25 and 60 μg/mL), inhibited cell proliferation (up to 81%), and tube formation (83% and 76%). In vivo treatment reduced body weight (50%); cell number (16.5- and 14.7-fold), secreted VEGF (∼90%), neoangiogenesis in rat cornea (2.5- and 1.5-fold) and CAM (3- and 1.6-fold) besides EAT cells accumulation in sub-G1 phase (20% and 18.38%), respectively.Discussion and conclusion: Considering the potent anti-angiogenic and pro-apoptotic properties, lead molecules from EA extracts of E. jambolana and M. paradisiaca can be developed into anticancer drugs.
Highlights
Angiogenesis involves the formation of new vasculature from the already existing blood vessels and is a characteristic phenomenon in numerous diseases, such as tumour formation, rheumatoid arthritis, diabetic retinopathy and psoriasis to name a few (Yu et al 2009; Miao et al 2011)
The effect of different plant extracts on the metabolic activity and the cytotoxicity was assessed by the MTT assay in MDA-MB-231 cells
Increasing concentrations of the four plant extracts were used and the effective concentration was calculated from the dose-response curve along with the IC50 values
Summary
Angiogenesis involves the formation of new vasculature from the already existing blood vessels and is a characteristic phenomenon in numerous diseases, such as tumour formation, rheumatoid arthritis, diabetic retinopathy and psoriasis to name a few (Yu et al 2009; Miao et al 2011). This physiological process is effected by various factors such as vascular endothelial growth factor (VEGF), angiopoietins (Ang), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP) which expedite cell proliferation, tube formation and migration of endothelial cells (Carmeliet & Jain 2011; Wang et al 2013). The majority of studies have shown that VEGF signalling in tumour cells is autocrine in nature, characteristic of more aggressive cancers, paracrine signalling occurs (Goel & Mercurio 2013)
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