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Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana,Musa paradisiaca,and Coccinia indica extracts
Authors:Harsha Raj M  Debidas Ghosh  Rita Banerjee
Institution:1. Department of Studies in Biotechnology, Molecular Oncology Lab, University of Mysore, Mysore, India;2. Department of Bio-Medical Laboratory Science &3. Management, Vidyasagar University, Midnapore, West Bengal, India;4. Department of Science &5. Technology, Government of India, New Delhi, India
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, 3H]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.
Keywords:Anti-angiogenic  pro-apoptotic  cytotoxicity
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