title: Abrus agglutinin is a potent anti-proliferative and anti-angiogenic agent in human breast cancer.
abstract: Abrus agglutinin (AGG), a plant lectin isolated from the seeds of Abrus precatorius, has documented antitumor and immunostimulatory effects in murine models. To examine possible antitumor activity against breast cancer, we established human breast tumor xenografts in athymic nude mice and intraperitoneally administered AGG. AGG inhibited tumor growth and angiogenesis as confirmed by monitoring the expression of Ki-67 and CD-31, respectively. In addition, TUNEL positive cells increased in breast tumors treated with AGG suggesting that AGG mediates anti-tumorigenic activity through induction of apoptosis and inhibition of angiogenesis. On a molecular level, AGG caused extrinsic apoptosis through ROS generation that was AKT-dependent in breast cancer cells, without affecting primary mammary epithelial cells, suggesting potential cancer specificity of this natural compound. In addition, using HUVECs, AGG inhibited expression of the pro-angiogenic factor IGFBP-2 in an AKT-dependent manner, reducing angiogenic phenotypes both in vitro and in vivo. Overall, the present results establish that AGG promotes both apoptosis and anti-angiogenic activities in human breast tumor cells, which might be exploited for treatment of breast and other cancers.
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhutia
authors.affiliation: Department of Biotechnology, Indian Institute of Technology, Kharagpur, India.
authors.forename: Birendra
authors.initials: B
authors.lastname: Behera
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Durgesh
authors.initials: D
authors.lastname: Nandini Das
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Subhadip
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Niharika
authors.initials: N
authors.lastname: Sinha
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Prashanta Kumar
authors.initials: PK
authors.lastname: Panda
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Prajna Paramita
authors.initials: PP
authors.lastname: Naik
authors.affiliation: Department of Life Science, National Institute of Technology, Rourkela, India.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Patra
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, India.
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Siddik
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Menezes
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Sarmistha
authors.initials: S
authors.lastname: Talukdar
authors.affiliation: Department of Biotechnology, Indian Institute of Technology, Kharagpur, India.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Maiti
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.|VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Swadesh K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.|VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.|VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.|VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.|VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D037121:Plant Lectins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018971:Insulin-Like Growth Factor Binding Protein 2; D037121:Plant Lectins; D017382:Reactive Oxygen Species; C016940:abrus agglutinin; D051057:Proto-Oncogene Proteins c-akt
keywords: Abrus; Akt; IGFBP-2; ROS; angiogenesis; apoptosis