ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics.

2.50
Hdl Handle:
http://hdl.handle.net/10146/64474
Title:
ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics.
Authors:
Roiz, Levava; Smirnoff, Patricia; Bar-Eli, Menashe; Schwartz, Betty; Shoseyov, Oded
Abstract:
BACKGROUND: ACTIBIND is an Aspergillus niger extracellular ribonuclease (T2-ribonuclease [RNase]) that possesses actin-binding activity. In plants, ACTIBIND inhibits the elongation and alters the orientation of pollen tubes by interfering with the intracellular actin network. The question rose whether ACTIBIND can also affect mammalian cancer development. METHODS: Cell colony formation was performed in human colon (HT-29, Caco-2, RSB), breast (ZR-75-1), and ovarian (2780) cancer cells in the presence or absence of 1 muM ACTIBIND. In HT-29 and ZR-75-1 cells, the effect of ACTIBIND on cell migration was studied by microscopic observations and by invasion assay through Matrigel. Tube formation was assessed in human umbilical vein endothelial cells (HUVEC) in the presence of angiogenin or basic fibroblast growth factor (bFGF) (1 microg/mL each) following overnight incubation with 1 or 10 microM ACTIBIND. In an athymic mouse xenograft model, HT-29 cells were injected subcutaneously, followed by subcutaneous (0.4-8 mg/mouse/injection) or intraperitoneal (0.001-1 mg/mouse/injection) injections of ACTIBIND. In a rat dimethylhydrazine (DMH)-colorectal carcinogenesis model, ACTIBIND was released directly into the colon via osmotic micropumps (250 microg/rat/day) or given orally via microcapsules (1.6 mg/rat/day). Aberrant crypt foci, tumors in the distal colon, and tumor blood vessels were examined. RESULTS: ACTIBIND had an anticlonogenic effect unrelated to its ribonuclease activity. It also inhibited angiogenin-induced HUVEC tube formation in a dose-responsive manner. ACTIBIND was found to bind actin in vitro. It also bound to cancer cell surfaces, leading to disruption of the internal actin network and inhibiting cell motility and invasiveness through Matrigel-coated filters. In mice, ACTIBIND inhibited HT-29 xenograft tumor development, given either as a subcutaneous or intraperitoneal treatment. In rats, ACTIBIND exerted preventive and therapeutic effects on developing colonic tumors induced by DMH. It also reduced the degree of tumor observation. CONCLUSIONS: This study indicated that ACTIBIND is an effective antiangiogenic and anticarcinogenic factor.
Citation:
Cancer 2006, 106 (10):2295-2308
Journal:
Cancer
Issue Date:
15-May-2006
URI:
http://hdl.handle.net/10146/64474
DOI:
10.1002/cncr.21878
PubMed ID:
16586499
Additional Links:
http://www3.interscience.wiley.com/journal/112579966/abstract?CRETRY=1&SRETRY=0
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: Agriculture;Angiogenesis Inhibitors;Animals;Anticarcinogenic Agents;Aspergillus niger;blood;Biopsy,Needle;Breast Neoplasms;cytology;Colorectal Neoplasms;dietary modulation of cancer & cancer biomarkers;drug effects;drug therapy;Disease Models,Animal;Endoribonucleases;Female;Food;Humans;Immunohistochemistry;Israel;lifestyle modulation of cancer & cancer biomarkers;Male;Mice;Mice,Nude;Neoplasm Transplantation;Neovascularization,Pathologic;pathology;pharmacology;prevention & control;Probability;Rats;Reference Values;Ribonucleases;Risk Factors;Sensitivity and Specificity;Transplantation,Heterologous;Tumor Cells,Cultured.
ISSN:
0008-543X
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorRoiz, Levava-
dc.contributor.authorSmirnoff, Patricia-
dc.contributor.authorBar-Eli, Menashe-
dc.contributor.authorSchwartz, Betty-
dc.contributor.authorShoseyov, Oded-
dc.date.accessioned2009-04-06T08:04:35Z-
dc.date.available2009-04-06T08:04:35Z-
dc.date.issued2006-05-15-
dc.identifier.citationCancer 2006, 106 (10):2295-2308en
dc.identifier.issn0008-543X-
dc.identifier.pmid16586499-
dc.identifier.doi10.1002/cncr.21878-
dc.identifier.urihttp://hdl.handle.net/10146/64474-
dc.descriptionKEYWORDS CLASSIFICATION: Agriculture;Angiogenesis Inhibitors;Animals;Anticarcinogenic Agents;Aspergillus niger;blood;Biopsy,Needle;Breast Neoplasms;cytology;Colorectal Neoplasms;dietary modulation of cancer & cancer biomarkers;drug effects;drug therapy;Disease Models,Animal;Endoribonucleases;Female;Food;Humans;Immunohistochemistry;Israel;lifestyle modulation of cancer & cancer biomarkers;Male;Mice;Mice,Nude;Neoplasm Transplantation;Neovascularization,Pathologic;pathology;pharmacology;prevention & control;Probability;Rats;Reference Values;Ribonucleases;Risk Factors;Sensitivity and Specificity;Transplantation,Heterologous;Tumor Cells,Cultured.en
dc.description.abstractBACKGROUND: ACTIBIND is an Aspergillus niger extracellular ribonuclease (T2-ribonuclease [RNase]) that possesses actin-binding activity. In plants, ACTIBIND inhibits the elongation and alters the orientation of pollen tubes by interfering with the intracellular actin network. The question rose whether ACTIBIND can also affect mammalian cancer development. METHODS: Cell colony formation was performed in human colon (HT-29, Caco-2, RSB), breast (ZR-75-1), and ovarian (2780) cancer cells in the presence or absence of 1 muM ACTIBIND. In HT-29 and ZR-75-1 cells, the effect of ACTIBIND on cell migration was studied by microscopic observations and by invasion assay through Matrigel. Tube formation was assessed in human umbilical vein endothelial cells (HUVEC) in the presence of angiogenin or basic fibroblast growth factor (bFGF) (1 microg/mL each) following overnight incubation with 1 or 10 microM ACTIBIND. In an athymic mouse xenograft model, HT-29 cells were injected subcutaneously, followed by subcutaneous (0.4-8 mg/mouse/injection) or intraperitoneal (0.001-1 mg/mouse/injection) injections of ACTIBIND. In a rat dimethylhydrazine (DMH)-colorectal carcinogenesis model, ACTIBIND was released directly into the colon via osmotic micropumps (250 microg/rat/day) or given orally via microcapsules (1.6 mg/rat/day). Aberrant crypt foci, tumors in the distal colon, and tumor blood vessels were examined. RESULTS: ACTIBIND had an anticlonogenic effect unrelated to its ribonuclease activity. It also inhibited angiogenin-induced HUVEC tube formation in a dose-responsive manner. ACTIBIND was found to bind actin in vitro. It also bound to cancer cell surfaces, leading to disruption of the internal actin network and inhibiting cell motility and invasiveness through Matrigel-coated filters. In mice, ACTIBIND inhibited HT-29 xenograft tumor development, given either as a subcutaneous or intraperitoneal treatment. In rats, ACTIBIND exerted preventive and therapeutic effects on developing colonic tumors induced by DMH. It also reduced the degree of tumor observation. CONCLUSIONS: This study indicated that ACTIBIND is an effective antiangiogenic and anticarcinogenic factor.en
dc.language.isoenen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/112579966/abstract?CRETRY=1&SRETRY=0en
dc.subjectACTIBINDen
dc.subjectActinen
dc.subjectAntiangiogenicen
dc.subjectAnticarcinogenicen
dc.subjectRibonucleaseen
dc.subject.meshAngiogenesis Inhibitors-
dc.subject.meshAnimals-
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshAspergillus niger-
dc.subject.meshBiopsy, Needle-
dc.subject.meshBreast Neoplasms-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshDisease Models, Animal-
dc.subject.meshEndoribonucleases-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshProbability-
dc.subject.meshRats-
dc.subject.meshReference Values-
dc.subject.meshRibonucleases-
dc.subject.meshRisk Factors-
dc.subject.meshSensitivity and Specificity-
dc.subject.meshTransplantation, Heterologous-
dc.subject.meshTumor Cells, Cultured-
dc.titleACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics.en
dc.typeArticleen
dc.identifier.journalCanceren

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