WO1997031107A3 - Human serum lectin - induced apoptosis and method for detecting apoptosis - Google Patents
Human serum lectin - induced apoptosis and method for detecting apoptosis Download PDFInfo
- Publication number
- WO1997031107A3 WO1997031107A3 PCT/CA1997/000101 CA9700101W WO9731107A3 WO 1997031107 A3 WO1997031107 A3 WO 1997031107A3 CA 9700101 W CA9700101 W CA 9700101W WO 9731107 A3 WO9731107 A3 WO 9731107A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- apoptosis
- cells
- proteins
- human
- present
- Prior art date
Links
- 230000006907 apoptotic process Effects 0.000 title abstract 6
- 102000004856 Lectins Human genes 0.000 title abstract 3
- 108090001090 Lectins Proteins 0.000 title abstract 3
- 239000002523 lectin Substances 0.000 title abstract 3
- 210000002966 serum Anatomy 0.000 title abstract 2
- 102000023852 carbohydrate binding proteins Human genes 0.000 abstract 2
- 108091008400 carbohydrate binding proteins Proteins 0.000 abstract 2
- 150000001720 carbohydrates Chemical class 0.000 abstract 2
- 235000014633 carbohydrates Nutrition 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 abstract 2
- 238000000338 in vitro Methods 0.000 abstract 2
- 102000004169 proteins and genes Human genes 0.000 abstract 2
- 108090000623 proteins and genes Proteins 0.000 abstract 2
- 206010006187 Breast cancer Diseases 0.000 abstract 1
- 208000026310 Breast neoplasm Diseases 0.000 abstract 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 abstract 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 abstract 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 abstract 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 abstract 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 abstract 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 abstract 1
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 abstract 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 abstract 1
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 abstract 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 230000002159 abnormal effect Effects 0.000 abstract 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 abstract 1
- 230000004075 alteration Effects 0.000 abstract 1
- 210000002403 aortic endothelial cell Anatomy 0.000 abstract 1
- 238000013459 approach Methods 0.000 abstract 1
- 238000003556 assay Methods 0.000 abstract 1
- DLRVVLDZNNYCBX-ZZFZYMBESA-N beta-melibiose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 DLRVVLDZNNYCBX-ZZFZYMBESA-N 0.000 abstract 1
- 230000027455 binding Effects 0.000 abstract 1
- 238000004166 bioassay Methods 0.000 abstract 1
- 239000008280 blood Substances 0.000 abstract 1
- 210000004369 blood Anatomy 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 230000030833 cell death Effects 0.000 abstract 1
- 230000001413 cellular effect Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229940127089 cytotoxic agent Drugs 0.000 abstract 1
- 239000002254 cytotoxic agent Substances 0.000 abstract 1
- 231100000599 cytotoxic agent Toxicity 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 210000002889 endothelial cell Anatomy 0.000 abstract 1
- 238000011156 evaluation Methods 0.000 abstract 1
- 230000013595 glycosylation Effects 0.000 abstract 1
- 238000006206 glycosylation reaction Methods 0.000 abstract 1
- 210000005260 human cell Anatomy 0.000 abstract 1
- 201000005202 lung cancer Diseases 0.000 abstract 1
- 208000020816 lung neoplasm Diseases 0.000 abstract 1
- 230000008506 pathogenesis Effects 0.000 abstract 1
- 230000037361 pathway Effects 0.000 abstract 1
- 230000009257 reactivity Effects 0.000 abstract 1
- 241000894007 species Species 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 210000004881 tumor cell Anatomy 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4726—Lectins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
Abstract
The unifying theme of the present invention is the description of a class of proteins present in human blood which have the capacity to selectively recognize and induce apoptosis of cells which convey abnormal surface carbohydrates. Alterations in cellular glycosylation can result from either species-specific differences or may reflect cancer-associated changes. Human serum carbohydrate binding proteins, referred to as lectins, were isolated on several different carbohydrate columns including Gal alpha (papGal), GalNAc, GlcNAc, Fucose, Mannose and Melibiose. These lectins were shown to cause apoptosis of porcine aortic endothelial cells. This demonstrates a new pathway leading to endothelial cell death following xenogenic stress that may be important in the pathogenesis of xenograft rejection and suggests new therapeutic approaches to the treatment of xenograft rejection. Further, these mammalian carbohydrate binding proteins are herein shown to cause apoptosis of breast cancer and lung cancer cells in vitro, and can be used as a cytotoxic agent against human tumour cells. Significantly, the proteins of the present invention exhibit minimal binding or reactivity against normally glycosylated human cells. This invention also relates to a novel bioassay for the detection and quantitation of cellular apoptosis in vitro, and to the utility of this assay for the identification and evaluation of compounds with potential apogenic activity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU15869/97A AU1586997A (en) | 1996-02-20 | 1997-02-19 | Human serum lectin - induced apoptosis and method for detecting apoptosis |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1196896P | 1996-02-20 | 1996-02-20 | |
| US60/011,968 | 1996-02-20 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1997031107A2 WO1997031107A2 (en) | 1997-08-28 |
| WO1997031107A3 true WO1997031107A3 (en) | 1997-11-27 |
Family
ID=21752745
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA1997/000101 WO1997031107A2 (en) | 1996-02-20 | 1997-02-19 | Human serum lectin - induced apoptosis and method for detecting apoptosis |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU1586997A (en) |
| WO (1) | WO1997031107A2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5948628A (en) | 1997-09-05 | 1999-09-07 | The Board Of Regents Of The University Of Oklahoma | Methods of screening for compounds which mimic galectin-1 |
| US5994298A (en) * | 1997-12-18 | 1999-11-30 | Tsai; David | Proteins for cancer cell specific induction of apoptosis and method for isolation thereof |
| US6737402B2 (en) | 1997-12-18 | 2004-05-18 | David Tsai | Method of preparing fetuin to induce apoptosis |
| MXPA00005954A (en) * | 1997-12-18 | 2002-09-18 | Tsai David | Proteins for cancer cell specific induction of apoptosis andmethod for isolation thereof. |
| US7238662B2 (en) | 1997-12-18 | 2007-07-03 | Ambryx Biotechnology, Inc. | Alpha 2HS glycoprotein for treatment of cancer and a method for preparation thereof |
| DE19806185C2 (en) * | 1998-02-02 | 1999-11-18 | Biogenes Gmbh | Immunoassay and test kit for the determination of fucosylated protein in a biological sample |
| AU7511800A (en) * | 1999-08-30 | 2001-03-26 | K.U. Leuven Research And Development | Novel target for antiparasitic agents and inhibitors thereof |
| US20090053740A1 (en) * | 2005-10-31 | 2009-02-26 | Cedars-Sinai Medical Center | Agglutination-based method for fast detection, isolation and quantification of apoptotic cells |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995015175A1 (en) * | 1993-12-05 | 1995-06-08 | Yeda Research And Development Co., Ltd. At The Weizmann Institute Of Science | Galectin-8 and galectin-8-like proteins and dna molecules coding therefor |
-
1997
- 1997-02-19 WO PCT/CA1997/000101 patent/WO1997031107A2/en active Application Filing
- 1997-02-19 AU AU15869/97A patent/AU1586997A/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995015175A1 (en) * | 1993-12-05 | 1995-06-08 | Yeda Research And Development Co., Ltd. At The Weizmann Institute Of Science | Galectin-8 and galectin-8-like proteins and dna molecules coding therefor |
Non-Patent Citations (8)
| Title |
|---|
| BUSSOLATI O ET AL: "Characterization of apoptotic phenomena induced by treatment with L-asparaginase in NIH3T3 cells.", EXP CELL RES, OCT 1995, 220 (2) P283-91, UNITED STATES, XP002041717 * |
| KULKARNI GV ET AL: "Serum deprivation induces apoptotic cell death in a subset of Balb/c 3T3 fibroblasts.", J CELL SCI, MAY 1994, 107 ( PT 5) P1169-79, ENGLAND, XP002041714 * |
| MATSUSHITA M ET AL: "A novel human serum lectin with collagen- and fibrinogen-like domains that functions as an opsonin", JOURNAL OF BIOLOGICAL CHEMISTRY, 271 (5). 02-02-1996. 2448-2454., XP000676762 * |
| NI Y ET AL: "LECTIN-CARBOHYDRATE INTERACTION IN THE IMMUNE-SYSTEM", VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 1996, 55, 205-223, XP002034770 * |
| PERILLO, NANCY L. ET AL: "Apoptosis of T cells mediated by galectin-1", NATURE (LONDON) (1995), 378(6558), 736-9 CODEN: NATUAS;ISSN: 0028-0836, XP002034768 * |
| SIT KH ET AL: "Reduced surface area in apoptotic rounding of human Chang liver cells from serum deprivation.", ANAT REC, DEC 1994, 240 (4) P456-68, UNITED STATES, XP002041715 * |
| WAWOTZNY R ET AL: "ARE MATRIX-IMMOBILIZED NEOGLYCOPROTEINS, PLANT AND HUMAN LECTINS AND CARBOHYDRATE-BINDING ANTIBODIES FROM HUMAN SERUM MEDIATORS OF ADHESION IN-VITRO FOR CARCINOMA AND LYMPHOSARCOMA CELLS", ANTICANCER RESEARCH, 1995, 15, 169-174, XP000676766 * |
| ZANETTA JP ET AL: "CARBOHYDRATES AND SOLUBLE LECTINS IN THE REGULATION OF CELL-ADHESION AND PROLIFERATION", HISTOLOGY AND HISTOPATHOLOGY, 1994, 9, 385-412, XP002034769 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1586997A (en) | 1997-09-10 |
| WO1997031107A2 (en) | 1997-08-28 |
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