Angiogenesis inhibitor
Encyclopedia
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis
). Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet
.
Angiogenesis inhibitors were once thought to have potential as a "silver bullet
" treatment applicable to many types of cancer, but this has not been the case in practice. Nonetheless, inhibitors are used to treat cancer, macular degeneration
in the eye, and other diseases that involve a proliferation of blood vessels.
When solid cancers are small, they are supplied with nutrients by diffusion from nearby blood vessels. In order to grow larger, they need their own blood vessels, which they create by angiogenesis promoters such as VEGF. Drugs that interrupt that process show promise in treating cancer. However, when one angiogenesis promoter is blocked, cancers eventually grow blood vessels using another angiogenesis promoter.
Angiogenesis inhibitors are also used to treat age-related macular degeneration, in which the blood vessels of the retina of the eye become overgrown and damage vision.
s or a dietary component
s. Some of them are endogenous as well.
(brand name Avastin), a kind of humanized mouse monoclonal antibody against vascular endothelial growth factor
(VEGF)
Through binding to VEGFR and other VEGF receptor in endothelial cells, VEGF can trigger multiple cellular responds like promoting cell survival, preventing apoptosis
, and remodeling cytoskeleton
, all of which promote angiogenesis.
Because it traps VEGF in the blood, bevacizumab
is an anti-angiogenesis factor. Lowering the concentration of VEGF results in reduced activation of the angiogenesis
pathway, thus inhibiting new blood vessel formation in tumors.
Research and development in this field has been driven largely by the desire to find better cancer
treatments. Tumors cannot grow larger than 2mm without angiogenesis
. By stopping the growth of blood vessels, scientists hope to cut the means by which tumors can nourish themselves and thus become metastasis
. After a series of clinical trials in 2004, Avastin got approval from the FDA, becoming the first commercially available anti-angiogenesis drug. FDA approval for breast cancer was later revoked on November 18, 2011.
Despite the therapeutic potential of anti-angiogenesis drugs, they also bring disasters when used inappropriately. The pharmaceutical thalidomide
is such an antiangiogenic agent. When pregnant women take an antiangiogenic agent, the developing fetus will not form blood vessels properly, thereby preventing the proper development of fetal limbs and circulatory systems. In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, most notably phocomelia
, as a consequence of thalidomide use.
In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as anti-obesity agents, as blood vessels in adipose tissue
never fully mature, and are thus destroyed by angiogenesis inhibitors.
Matrix metalloproteinase inhibitor
s that may be antiangiogenic are batimastat and marimastat
.
According to a study published in the August 15, 2004 issue of the journal Cancer Research, cannabinoids
, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
, the prevention of metastasis
through the inhibition of angiogenesis
. In particular, the following foodstuffs contain significant inhibitors and have been suggested as part of a healthy diet for this and other benefits:
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
). Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
.
Angiogenesis inhibitors were once thought to have potential as a "silver bullet
Silver bullet
In folklore, the silver bullet is supposed to be the only kind of bullet for firearms that is effective against a werewolf, witch, or other monsters...
" treatment applicable to many types of cancer, but this has not been the case in practice. Nonetheless, inhibitors are used to treat cancer, macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
in the eye, and other diseases that involve a proliferation of blood vessels.
When solid cancers are small, they are supplied with nutrients by diffusion from nearby blood vessels. In order to grow larger, they need their own blood vessels, which they create by angiogenesis promoters such as VEGF. Drugs that interrupt that process show promise in treating cancer. However, when one angiogenesis promoter is blocked, cancers eventually grow blood vessels using another angiogenesis promoter.
Angiogenesis inhibitors are also used to treat age-related macular degeneration, in which the blood vessels of the retina of the eye become overgrown and damage vision.
Endogenous
| Inhibitors | Mechanism |
|---|---|
| soluble VEGFR-1 and NRP-1 | decoy receptors for VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... -B and PIGF PIGF Phosphatidylinositol-glycan biosynthesis class F protein is a protein that in humans is encoded by the PIGF gene.-Further reading:... |
| Angiopoietin 2 | antagonist of angiopoietin 1 Angiopoietin 1 Angiopoietin 1 is a type of angiopoietin and is encoded by the gene ANGPT1.-Interactions:Angiopoietin 1 has been shown to interact with TEK tyrosine kinase.-Further reading:... |
| TSP-1 and TSP-2 Thrombospondin Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... , cell proliferation, cell adhesion Cell adhesion Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure... and survival of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| angiostatin Angiostatin Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor , and it is currently undergoing clinical trials for its use in anticancer therapy.-Structure:Angiostatin is a 38 kDa fragment of a larger protein, plasmin ... and related molecules |
inhibit cell proliferation and induce apoptosis Apoptosis Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation... of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| endostatin Endostatin ]Endostatin is a naturally-occurring 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... , cell proliferation and survival of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| vasostatin, calreticulin Calreticulin Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 is a protein that in humans is encoded by the CALR gene.... |
inhibit cell proliferation of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| platelet factor-4 | inhibits binding of bFGF and VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... |
| TIMP Tissue inhibitor of metalloproteinases The matrix metalloproteinases are inhibited by specific endogenous tissue inhibitors of metalloproteinases , which comprise a family of four protease inhibitors: TIMP1, TIMP2, TIMP3 and TIMP4.... and CDAI Cartilage-derived angiogenesis inhibitor A cartilage-derived angiogenesis inhibitor is an angiogenesis inhibitor produced from cartilage. Examples include the peptide troponin I and chondromodulin I.The antiangiogenic effect may be an inhibition of basement membrane degradation.... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| Meth-1 and Meth-2 | |
| IFN-α, -β and -γ, CXCL10 CXCL10 C-X-C motif chemokine 10 also known as Interferon gamma-induced protein 10 or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene... , IL-4 Interleukin 4 Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent... , -12 Interleukin 12 Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:... and -18 Interleukin 18 Interleukin-18 also known as IL18 is a protein which in humans is encoded by the IL18 gene. The protein encoded by this gene is a proinflammatory cytokine.- Function :... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... , downregulate bFGF |
| prothrombin (kringle domain Kringle domain Kringle Domains are autonomous protein domains that fold into large loops stabilized by 3 disulfide linkages. These are important in protein-protein interactions with blood coagulation factors... -2), antithrombin III fragment |
inhibit cell proliferation of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| prolactin Prolactin Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen... |
inhibit bFGF and VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... |
| VEGI | affects cell proliferation of endothelial cells Endothelium The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart... |
| SPARC SPARC SPARC is a RISC instruction set architecture developed by Sun Microsystems and introduced in mid-1987.... |
inhibit binding and activity of VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... |
| osteopontin Osteopontin Osteopontin , also known as bone sialoprotein I , early T-lymphocyte activation , secreted phosphoprotein 1 , 2ar and Rickettsia resistance , is a human gene product, which is also conserved in other species... |
inhibit integrin Integrin Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle.... signalling |
| maspin Maspin Maspin is a serpin and tumor suppressor gene.It has been associated with prostate cancer and breast cancer.It has also been associated with tumors of the pancreas.It was identified in 1994.-Further reading:-External links:... |
inhibits proteases |
| canstatin | |
| proliferin-related protein | |
| restin |
Exogenous
Exogenous angiogenesis inhibitors may be drugMedication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s or a dietary component
Diet (nutrition)
In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
s. Some of them are endogenous as well.
Drugs
Known inhibitors include the drug bevacizumabBevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
(brand name Avastin), a kind of humanized mouse monoclonal antibody against vascular endothelial growth factor
Vascular endothelial growth factor
Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
(VEGF)
Through binding to VEGFR and other VEGF receptor in endothelial cells, VEGF can trigger multiple cellular responds like promoting cell survival, preventing apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
, and remodeling cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
, all of which promote angiogenesis.
Because it traps VEGF in the blood, bevacizumab
Bevacizumab
Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....
is an anti-angiogenesis factor. Lowering the concentration of VEGF results in reduced activation of the angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
pathway, thus inhibiting new blood vessel formation in tumors.
Research and development in this field has been driven largely by the desire to find better cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
treatments. Tumors cannot grow larger than 2mm without angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
. By stopping the growth of blood vessels, scientists hope to cut the means by which tumors can nourish themselves and thus become metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
. After a series of clinical trials in 2004, Avastin got approval from the FDA, becoming the first commercially available anti-angiogenesis drug. FDA approval for breast cancer was later revoked on November 18, 2011.
Despite the therapeutic potential of anti-angiogenesis drugs, they also bring disasters when used inappropriately. The pharmaceutical thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
is such an antiangiogenic agent. When pregnant women take an antiangiogenic agent, the developing fetus will not form blood vessels properly, thereby preventing the proper development of fetal limbs and circulatory systems. In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, most notably phocomelia
Phocomelia
Phocomelia is an extremely rare congenital disorder involving the limbs . Étienne Geoffroy Saint-Hilaire coined the term in 1836....
, as a consequence of thalidomide use.
In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as anti-obesity agents, as blood vessels in adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
never fully mature, and are thus destroyed by angiogenesis inhibitors.
Matrix metalloproteinase inhibitor
Matrix metalloproteinase inhibitor
A matrix metalloproteinase inhibitor inhibits matrix metalloproteinases. As they inhibit cell migration they have antiangiogenic effects. They may be both endogenous and exogenous....
s that may be antiangiogenic are batimastat and marimastat
Marimastat
Marimastat was a proposed antineoplastic drug developed by British Biotech. It acted as a broad-spectrum matrix metalloproteinase inhibitor.Marimastat performed poorly in clinical trials, and development was terminated....
.
According to a study published in the August 15, 2004 issue of the journal Cancer Research, cannabinoids
Cannabinoids
Cannabinoids are a class of chemical compounds that include the phytocannabinoids , and chemical compounds that mimic the actions of phytocannabinoids or have a similar structure...
, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).
| Inhibitors | Antiangiogenic use in | Mechanism |
|---|---|---|
| bevacizumab Bevacizumab Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas.... |
Cancer | binds VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... |
| itraconazole Itraconazole Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:... |
Cancer | inhibits VEGFR phosphorylation, glycosylation Glycosylation Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules... , mTOR signaling, endothelial cell proliferation, cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... , tube formation, and tumor associated angiogenesis. |
| carboxyamidotriazole | inhibit cell proliferation and cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... of endothelial cells |
|
| TNP-470 | ||
| CM101 | activate immune system Immune system An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own... |
|
| IFN-α | downregulate angiogenesis stimulators and inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... of endothelial cells |
|
| IL-12 Interleukin 12 Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:... |
stimulate angiogenesis inhibitor formation | |
| platelet factor-4 | inhibits binding of angiogenesis stimulators | |
| suramin Suramin Suramin is a drug developed by Oskar Dressel and Richard Kothe of Bayer, Germany in 1916, and is still sold by Bayer under the brand name Germanin.According to the National Cancer Institute there are no active clinical trials... |
prostate cancer | |
| SU5416 | ||
| thrombospondin Thrombospondin Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins... |
||
| VEGFR antagonists | ||
| angiostatic steroids + heparin Heparin Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule... |
inhibit basement membrane Basement membrane The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :... degradation |
|
| Cartilage-Derived Angiogenesis Inhibitory Factor | ||
| matrix metalloproteinase inhibitors | ||
| angiostatin Angiostatin Angiostatin is a naturally occurring protein found in several animal species, including humans. It is an endogenous angiogenesis inhibitor , and it is currently undergoing clinical trials for its use in anticancer therapy.-Structure:Angiostatin is a 38 kDa fragment of a larger protein, plasmin ... |
inhibit cell proliferation and induce apoptosis Apoptosis Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation... of endothelial cells |
|
| endostatin Endostatin ]Endostatin is a naturally-occurring 20-kDa C-terminal fragment derived from type XVIII collagen. It is reported to serve as an anti-angiogenic agent, similar to angiostatin and thrombospondin.... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... , cell proliferation and survival of endothelial cells |
|
| 2-methoxyestradiol 2-Methoxyestradiol 2-Methoxyestradiol is a drug that prevents the formation of new blood vessels that tumors need in order to grow . It is derived from estrogen, although it binds poorly to known estrogen receptors, and belongs to the family of drugs called angiogenesis inhibitors... |
inhibit cell proliferation and cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... and induce apoptosis Apoptosis Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation... of endothelial cells |
|
| tecogalan | inhibit cell proliferation of endothelial cells | |
| tetrathiomolybdate | Cancer | copper chelation which inhibits blood vessel growth |
| thalidomide Thalidomide Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used... |
inhibit cell proliferation of endothelial cells | |
| thrombospondin Thrombospondin Thrombospondins are secreted proteins with antiangiogenic abilities. TSP was discovered by Nancy L. Baenziger.-Types:The thrombospondins are a family of multifunctional proteins... |
inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... , cell proliferation, cell adhesion Cell adhesion Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure... and survival of endothelial cells |
|
| prolactin Prolactin Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen... |
inhibit bFGF and VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate.... |
|
| αVβ3 Alpha-v beta-3 αVβ3 is a type of integrin that is a receptor for vitronectin. It consists of two components, integrin alpha V and integrin beta 3 , and is expressed by platelets. Furthermore it is a receptor for phagocytosis on macrophages or dendritic cells.... inhibitors |
induce apoptosis Apoptosis Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation... of endothelial cells |
|
| linomide | inhibit cell migration Cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations... of endothelial cells |
|
Diet
Some common components of human diets also act as mild angiogenesis inhibitors and have therefore been proposed for angiopreventionAngioprevention
Angioprevention is the concept of preventing disease development or progression through the inhibition of angiogenesis, the process of forming blood vessels. The concept of angioprevention has been developed by Adriana Albini and co-workers who showed that several drugs and natural compounds for...
, the prevention of metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
through the inhibition of angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
. In particular, the following foodstuffs contain significant inhibitors and have been suggested as part of a healthy diet for this and other benefits:
- Soy products such as tofuTofuis a food made by coagulating soy milk and then pressing the resulting curds into soft white blocks. It is part of East Asian and Southeast Asian cuisine such as Chinese, Japanese, Korean, Indonesian, Vietnamese, and others. There are many different varieties of tofu, including fresh tofu and tofu...
and tempehTempehTempeh , or tempe , is a traditional soy product originally from Indonesia. It is made by a natural culturing and controlled fermentation process that binds soybeans into a cake form, similar to a very firm vegetarian burger patty...
, (which contain the inhibitor "genisteinGenisteinGenistein is one of several known isoflavones. Isoflavones, such as genistein and daidzein, are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plant, Flemingia vestita and coffee Besides functioning as...
") - Agaricus blazeiAgaricus blazeiAgaricus subrufescens is a species of mushroom, commonly known as almond mushroom, mushroom of the sun, God's mushroom, mushroom of life, royal sun agaricus, jisongrong or himematsutake and by a number of other...
mushrooms (angiogenesis inhibitors found in the mushroom include sodium pyroglutamatePyroglutamic acidPyroglutamic acid is an uncommon amino acid derivative in which the free amino group of glutamic acid cyclizes to form a lactam. It is found in many proteins including bacteriorhodopsin. N-terminal glutamine residues can spontaneously cyclize to become pyroglutamate...
and ergosterolErgosterolErgosterol is a sterol found in fungi, and named for ergot, a common name for the members of the fungal genus Claviceps from which ergosterol was first isolated. Ergosterol does not occur in plant or animal cells...
) - Black raspberryRubus occidentalisRubus occidentalis is a species of Rubus native to eastern North America. Its common name black raspberry is shared with the closely related western American species Rubus leucodermis...
extract (Rubus occidentalis) - Reishi mushrooms (via inhibition of VEGFVascular endothelial growth factorVascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
and TGF-beta) - Trametes versicolorTrametes versicolorTrametes versicolor — formerly known as Coriolus versicolor and Polyporus versicolor — is an extremely common polypore mushroom which can be found throughout the world. Versicolor means 'of several colours' and it is true that this mushroom is found in a wide variety of different colours. T...
mushrooms - Maitake mushrooms (via inhibition of VEGFVascular endothelial growth factorVascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....
) - Phellinus linteusPhellinus LinteusPhellinus linteus is a medicinal mushroom used in Japan, Korea and China. It is shaped like a hoof, has a bitter taste, and in the wild grows on mulberry trees. The stem's color ranges from dark brown to black...
mushrooms - Green teaGreen teaGreen tea is made solely from the leaves of Camellia sinensis that have undergone minimal oxidation during processing. Green tea originates from China and has become associated with many cultures throughout Asia. It has recently become more widespread in the West, where black tea is traditionally...
(catechins) - Liquorice (glycyrrhizic acid)
- Red Wine (resveratrolResveratrolResveratrol is a stilbenoid, a type of natural phenol, and a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi....
) - Bananas produces a substance known as TNFTumor necrosis factorsTumor necrosis factors refers to a group of cytokines family that can cause cell death . The first two members of the family to be identified were:...
which combats cancer cells. - Antiangiogenic phytochemicals and medicinal herbs.
- Royal JellyRoyal jellyRoyal jelly is a honey bee secretion that is used in the nutrition of larvae, as well as adult queens. It is secreted from the glands in the hypopharynx of worker bees, and fed to all larvae in the colony....
External links
- Angiogenesis Inhibitors for Cancer - from The Angiogenesis Foundation, 23 June 2009
- Angiogenesis Inhibitors for Eye Disease - from The Angiogenesis Foundation, 23 June 2009
- Angiogenesis Inhibitors in the Treatment of Cancer - from the National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
- New Scientist on their use as fat-reducing drugs - from New ScientistNew ScientistNew Scientist is a weekly non-peer-reviewed English-language international science magazine, which since 1996 has also run a website, covering recent developments in science and technology for a general audience. Founded in 1956, it is published by Reed Business Information Ltd, a subsidiary of...
, 10 April 2004