Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts

Pharm Biol. 2017 Dec;55(1):1489-1499. doi: 10.1080/13880209.2017.1307422.

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.

Keywords: Anti-angiogenic; cytotoxicity; pro-apoptotic.

MeSH terms

  • 1-Butanol / chemistry
  • Acetates / chemistry
  • Angiogenesis Inhibitors / isolation & purification
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Ehrlich Tumor / blood
  • Carcinoma, Ehrlich Tumor / pathology
  • Carcinoma, Ehrlich Tumor / prevention & control*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply*
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / physiopathology
  • Corneal Neovascularization / prevention & control
  • Cucurbitaceae / chemistry*
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • MCF-7 Cells
  • Mice
  • Musa / chemistry*
  • Neovascularization, Pathologic*
  • Neovascularization, Physiologic / drug effects*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Plant Roots / chemistry
  • Plants, Medicinal
  • Rats, Wistar
  • Seeds / chemistry
  • Syzygium / chemistry*
  • Time Factors
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Acetates
  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • ethyl acetate
  • 1-Butanol

Grants and funding

The University Grants Commission Special Assistance Programme Department of Special Assistance (UGC-SPA-DSA) Government of India [No. f 4-1/2013(SAP-II)] is acknowledged.