title: Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts.
abstract: BACKGROUND
  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.
  
  
  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 (IC5025 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Studies in Biotechnology , Molecular Oncology Lab, University of Mysore , Mysore , India.
authors.forename: Harsha Raj
authors.initials: HR
authors.lastname: M
authors.affiliation: b Department of Bio-Medical Laboratory Science & Management , Vidyasagar University , Midnapore , West Bengal , India.
authors.forename: Debidas
authors.initials: D
authors.lastname: Ghosh
authors.affiliation: c Department of Science & Technology , Government of India , New Delhi , India.
authors.forename: Rita
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: a Department of Studies in Biotechnology , Molecular Oncology Lab, University of Mysore , Mysore , India.
authors.forename: Bharathi P
authors.initials: BP
authors.lastname: Salimath
mesh_terms: D020001:1-Butanol / Q000737:chemistry; D000085:Acetates / Q000737:chemistry; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D016510:Corneal Neovascularization / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D019662:Cucurbitaceae / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D028521:Musa / Q000737:chemistry*; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D027842:Syzygium / Q000737:chemistry*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D000085:Acetates; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C007650:ethyl acetate; D020001:1-Butanol
keywords: Anti-angiogenic; cytotoxicity; pro-apoptotic