title: Immunomodulatory glc/man-directed Dolichos lablab lectin (DLL) evokes anti-tumour response in vivo by counteracting angiogenic gene expressions.
abstract: Neovascularization and jeopardized immunity has been critically emphasized for the establishment of malignant progression. Lectins are the diverse class of carbohydrate interacting proteins, having great potential as immunopotentiating and anti-cancer agents. The present investigation sought to demonstrate the anti-proliferative activity of Dolichos lablab lectin (DLL) encompassing immunomodulatory attributes. DLL specific to glucose and mannose carbohydrate moieties has been purified to homogeneity from the common dietary legume D. lablab. Results elucidated that DLL agglutinated blood cells non-specifically and displayed striking mitogenicity to human and murine lymphocytes in vitro with interleukin (IL)-2 production. The DLL-conditioned medium exerted cytotoxicity towards malignant cells and neoangiogenesis in vitro. Similarly, in-vivo anti-tumour investigation of DLL elucidated the regressed proliferation of ascitic and solid tumour cells, which was paralleled with blockade of tumour neovasculature. DLL-treated mice showed an up-regulated immunoregulatory cytokine IL-2 in contrast to severely declined levels in control mice. Mechanistic validation revealed that DLL has abrogated the microvessel formation by weakening the proangiogenic signals, specifically nuclear factor kappa B (NF-κB), hypoxia inducible factor 1α (HIF-1 α), matrix metalloproteinase (MMP)-2 and 9 and vascular endothelial growth factor (VEGF) in malignant cells leading to tumour regression. In summary, it is evident that the dietary lectin DLL potentially dampens the malignant establishment by mitigating neoangiogenesis and immune shutdown. For the first time, to our knowledge, this study illustrates the critical role of DLL as an immunostimulatory and anti-angiogenic molecule in cancer therapeutics.
authors.affiliation: Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.|Laboratory for Immunomodulation and Inflammation Biology, Department of Studies and Research in Biochemistry, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Vigneshwaran
authors.affiliation: Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.
authors.forename: P
authors.initials: P
authors.lastname: Thirusangu
authors.affiliation: Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.|Department of Pharmacology and Centre for Lung and Vascular Biology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Vijay Avin
authors.affiliation: Postgraduate Department of Studies and Research in Biotechnology and Bioinformatics, Kuvempu University, Shankaraghatta, Shivamogga, Karnataka, India.
authors.forename: V
authors.initials: V
authors.lastname: Krishna
authors.affiliation: Laboratory for Immunomodulation and Inflammation Biology, Department of Studies and Research in Biochemistry, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.
authors.forename: S N
authors.initials: SN
authors.lastname: Pramod
authors.affiliation: Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College (Autonomous), Kuvempu University, Shivamogga, Karnataka, India.
authors.forename: B T
authors.identifier: 0000-0003-2377-9179
authors.initials: BT
authors.lastname: Prabhakar
mesh_terms: D000072283:A549 Cells; D000371:Agglutination; D000818:Animals; D001011:Aorta / Q000187:drug effects; D018929:Cell Culture Techniques; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D004187:Disaccharides; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D056747:Immunomodulation; D007376:Interleukin-2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000276:immunology / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D037121:Plant Lectins / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D004187:Disaccharides; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007376:Interleukin-2; D008934:Mitogens; D037121:Plant Lectins; D042461:Vascular Endothelial Growth Factor A; C442499:dolichos Lablab lectin; C095558:4-glucopyranosylmannose; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9
keywords: Dolichos lablab lectin; anti-tumour; immunomodulation; mitogenecity; tumour neovasculature