MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Inhibice angiogeneze

(-)-epigallocatechin-3-gallate (EGCG)

  • Major green tea catechin
  • Suppressed endothelial cell proliferation, migration, and tube formation:
    • Inhibiting PI3K/AKT and MEK/ERK pathways
    • Activation of FOXO transcription factors in HUVECs
  • EGCG also activated a TRPV1-Ca2+ signaling pathway and its downstream molecules
    • Akt, AMPK, calmodulin-dependent protein kinase II (CaMKII), and eNOS activation, as well as NO production in a Matrigel plugs mice model
  • EGCG inhibited tumor growth, proliferation, migration, and angiogenesis of a breast cancer xenograft in a mice model
    • Suppression of HIF1alpha, VEGF, and NFkappaB
  • Inhibition of cancer cell proliferation via
    • Ki67 and PCNA, apoptotic induction with increased cleavage of caspase-3,
    • Reduction of ERK activity,
    • Enhancement of p38 and JNK activities
  • Restricted angiogenesis via inhibiting
    • VWF, VEGF, and CD31,
  • Inhibited metastasis via inhibiting
    • MMP2, MMP7, MMP9, and MMP12
  • Upregulated Bim and cell cycle arrest marker p27/KIP1
  • Activated the cleavage of caspase-3
  • Anti-angiogenic effects of EGCG were through inhibition of
    • CD31, VEGF, neuropilin, IL6, IL8, SEMA3F, and HIF1alpha
  • Some EGCG derivatives have anti-angiogenic activities

Methylated-(3”)-epigallocatechin gallate analog (MethylEGCG)

  • Inhibited the activity of VEGF-dependent VEGFR2 and JNK,
    • Cell proliferation, and tube formation in HUVECs.
  • MethylEGCG suppressed growth Huh7 hepatoma xenografted in mice by reducing CD31-positive cells in blood vessels
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG)

  • Anti-angiogenic effects in endometrial cancer
  • Pro-EGCG suppressed tumor angiogenesis through
    • Decreasing VEGFA and HIF1alpha in tumor cells
    • Inhibiting a PI3K/AKT/mTOR/ HIF1alpha pathway
  • Reduced the migration and differentiation of VEGFA-expressing tumor-associated macrophages
    • Inhibition of chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Nevhodné medikamenty při hypoperfuzi míchy

.nevhodne-medikamenty.jpg

Allium ascalonicum - šalotka

  • Heat-stable and flavonoid-rich fraction of shallot extract
  • Potently showed anti-angiogenic effect

Aloe barbadensis (aloe vera leaf and pulp extracts)


Andrographolide

  • From Andrographis paniculata (Burm. f.) Nees
  • Anti-angiogenic effect
  • Inhibition of cell growth, migration, and tube formation in a HUVEC cell model
  • Inhibition of blood vessel formation in a CAM model.
  • Viva decreasing the expression of miR-21 (a short noncoding RNA)
    • Targeting of TIMP3 and suppressing the expression of MMP9
  • Andrographolide also inhibited MMP2 and MMP9-mediated metastasis in vitro
  • Regulated the nuclear translocation of transcription factors such as p65, p50, and NFkappaB, c-fos, activated transcription factor-2, and cyclic adenosine monophosphate (cAMP) response element-binding protein
  • Also inhibited tumor vessels and tumor growth against Hep3B cancer cells xenografted in nude mice
    • Inhibition of VEGFA/ VEGFR2 and its downstream MAPK signaling
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Angelica sinensis (aqueous extracts)

Angelica sinensis (dong quai)

Angiotensin-(1-7)


Arginin při deficitu BH4

  • Results suggest that in the absence of BH4, the introduction of L-arginine
    • May induce conformational changes in eNOS that promote electron flow and increase superoxide production if BH4 is not available
      • To couple oxygen activation to L-arginine oxidation
  • Observation that L-arginine dose-dependently increases NADPH consumption by BH4-depleted eNOS

Artemisia annua (Chinese wormwood)


Artemisia annua (artemisinin)


Barbigerone

  • Isoflavone from the seed of Millettia dielsiena
  • A dietary plant in southern China
  • Significantly suppressed angiogenesis in a zebrafish model and Matrigel plug model
  • It inhibited VEGF-induced cell proliferation, migration, and tube formation in HUVECs via
    • Deactivation of VEGFR2, followed by blocking of downstream kinases,
      • Focal adhesion kinase (FAK),
      • AKT, ERK, and p38,
      • Expression of inducible nitric oxide synthase (iNOS)
  • Barbigerone-inhibited tumor growth against human non-small-cell lung cancer (NSCLC) xenografted in a mice model
    • Mediated through a VEGFR2 signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Ze semene a luštěniny Tephrosia barbigera
  • Členové rod Millettia jsou bohaté na barbigeron, včetně:
    • M. dielsiena
    • M. ferruginea
    • M. usaramensis
    • M. pachycarpa
  • Z léčivé rostliny Sarcolobus globosus
  • cs.vvikipedla.com/wiki/Barbigerone

Berberis paraspecta Root - druh dřišťálu

Edible berries

  • Contain high concentrations of proanthocyanidin
  • Inhibits vegf expression induced by tumour necrosis factor alpha (tnfalpha)
  • Feeding proanthocyanidins to mice with tumour xenografts reduced vegf secretion, which resulted in reduced intratumoral microvasculature
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Beta-carotene

  • Able to block cell proliferation, migration, and tube formation of endothelial cells by
    • Downregulating the expression of MMP2, MMP9, prolyl hydroxylase, and lysyl oxidase
    • Upregulating the expression of TIMP1 and TIMP2.
  • In B16F-10 tumor-bearing mice beta-carotene decreased formation of tumor-directed capillaries
    • Altered serum cytokine levels
    • Decreased nuclear translocation of transcription factors
      • P65, p50, NF?B, c-fos, activated transcription factor-2, and cAMP response­element-binding protein
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Blokátory Bcl

  • BCL2 and TP53 geny regulují VEGF angiogenezi
  • Curcumin
  • Green tea extract
  • Šišák bajkalský - Scutellaria baicalensis - baicalin, baicalein, wogenin,and oroxylin
    • Inhibit BCL2 overexpression, plus COX2 gene expression and NF-kappa B activation
  • Ibišek - Hibiscus protocatechuic acid - from the dried flower of Hibiscus sabdariffa L.;
    • Inhibits Bcl-2 activity
  • Rybí tuk
    • EPA from fish oil
  • Jmelí
  • Viscum album (mistletoe)
    • Lectin extract
  • Zázvor
    • 6-gingerol
  • Grepová semínka - grape seed extract
  • Ženšen
    • Echinocystic acid (a triterpene found in ginseng and other Asianherbs)
  • Řimbaba
    • Parthenolide (a sesquiterpene lactonefound in feverfew)
  • Lapáčo
    • Beta-lapachone (a quinoneobtained from the bark of the lapacho tree)
  • www.researchgate.net/publication/6261578_Natural_Health_Products_That_Inhibit_Angiogenesis_A_Potential_Source_for_Investigational_New_Agents_to_Treat_Cancer-Part_2 [accessed Jun 11 2021].

Bovine cartilage


Caffeine

  • Inhibited angiogenesis through downregulating expression of
    • VEGF, VEGFR2, PIGF, IGF2, NRP1,
    • VE-cadherin(+),
  • Upregulating expression of
    • Ang1 and Ang2
  • In zebrafish model, caffeine disturbed
    • The vessel development
      • In ISVs, dorsal longitudinal anastomotic vessels
    • SIV sprouting
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Camellia sinensis (epigallocatechin)

  • Camellia sinensis (green tea) Contains 95 % phenols; 50% epigallocatechin
  • Herbs and their derivatives that specifically inhibit vascular endothelial growth factor and have direct activity against angiogenesis
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Catharanthus roseus Leaf - Barvínkovec růžový list

Chlorogenic acid - 5-O-caffeoylquinic acid

  • One of the most abundant polyphenol compounds in the human diet
  • Major compound in coffee
  • Plants such as honeysuckle and Eucommia
  • Anti-angiogenic effect of chlorogenic acid in HUVECs
    • Reducing expression of angiogenic markers
      • Endoglin,
      • Endothelin-1, ANG2, MMP2, FAK, IL8, VEGFR2-mediated phosphorylation of ERK1/2
      • Serine–threonine kinases
  • Blocked VEGF-stimulated angiogenesis in a Matrigel plug mice model via
    • Inhibition of a HIF1alpha/VEGF/AKT/ERK signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Highest contents of chlorogenic acid, rosmarinic acid, and caffeic acid
    • Lonicera japonica flowering buds
    • Melissa officinalis leaves
    • Coffea canephora seeds

Choerospondias axillaris fruit peels

  • Proanthocyanidins - potent anti-angiogenic activity
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Chrysin (5,7-dihydroxyflavone)

  • Significantly inhibited IL6-induced neovascularization in a CAM model
  • Chrysin also inhibited cell migration and tube formation in HUVECs by:
    • Modulation of an IL6 receptor/glycoprotein 130 (gp130)/JAK1/STAT3/VEGF signaling pathway
  • In DU145 xenograft-induced angiogenesis in a nude mice model, chrysin inhibited tumor-induced angiogenesis by
    • Decreasing the activation and expression of HIF1alpha/VEGF
    • Interaction between HIF1alpha and heat shock protein 90
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Chrysobalanus icaco (methanol extract)

Conjugated linoleic acid (CLA) - Konjugovaná kyselina linolová

  • Inhibit rat mammary carcinogenesis
    • Decreased proliferation and induction of apoptosis
  • Decrease the ability of mammary stromal cells to form complex anastomosing microcapillary networks in vitro
    • CLA might inhibit angiogenesis in vivo
  • CD2/F(1) mice were placed on synthetic diets containing 0, 1, or 2% CLA for 6 weeks
    • After angiogenic challenge by s.c. injection with an angiogenic gel substrate (Matrigel pellet assay)
    • After 7 days, the pellets from animals fed the control diet were infiltrated by abundant branching networks of blood vessels
      • With patent lumen-containing RBCs
  • Pellets from the CLA-fed animals contained fewer infiltrating cells
    • Formed limited branching cellular networks
    • Majority of which had collapsed lumen and no RBCs
  • Dietary CLA decreased
    • Serum levels of vascular endothelial growth factor (VEGF)
    • Whole mammary gland levels of VEGF and its receptor Flk-1
  • Cis-9, trans-11 and trans-10, cis-12 CLA isomers
    • Were effective in inhibiting angiogenesis in vitro in a dose-dependent fashion
  • pubmed.ncbi.nlm.nih.gov/12154044/

Copper Antagonists

  • Role of copper in cancer promotion through pro-inflammatory cascades and angiogenesis induction is quite well established
  • Essential for the function of many angiogenic growth factors
    • Bfgf, vegf, tnf?, and il-1 are copper-dependent !!
  • Copper chelation with tetrathiomolybdate
    • Promising therapy for tumour control
    • Inhibits multiple angiogenic cytokines
  • Several aromatic herbs—such as
    • Caryophylli flos,
    • Cinnamomi cortex
    • Foeniculi fructus
    • Zedoariae rhizoma
  • Have inhibitory effects on lipid peroxidation or protein oxidative modification by copper
    • They may have a role to play in anti-angiogenesis, but further research is necessary for confirmation
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Coptis chinensis Rhizome


Cucurbitacin B (CuB)

  • Triterpenoid
  • In some plants of the Cucurbitaceae family, including
    • Pumpkins
    • Gourds
  • Antiangiogenic effects of CuB
    • Suppress cell migration, invasion, and tube formation in HUVECs
    • Reduce preexisting vasculature in a CAM model and Matrigel plug mice model
  • CuB possessed a strong antimigration and anti-invasive ability against metastatic NSCLC
    • Downregulation of the Wnt/beta-catenin signaling pathway
  • The strong anti-metastatic capacity of CuB
    • In a highly metastatic 4T1-syngeneic mouse mammary cancer
      • Inhibition of tumor growth, lung metastasis, and angiogenesis
        • Downregulation of VEGF/FAK/MMP9 signaling pathway and CD31 (marker neoangiogeneze)
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Cucurbitacin B. z
    • Hemsleya endecaphylla (62 mg / 72 g)
    • Cucurbita andreana
    • 2-O-glukosid, z Begonia heracleifolia
  • 23,24-dihydrocucurbitacin B z
    • Hemsleya endecaphylla, 49 mg / 72 g
    • Z kořenů Picrorhiza kurrooa - Kutki
  • Deacetoxycucurbitacin B 2-O-glukosid
    • Z kořenů Picrorhiza kurrooa [1]:5
  • Isocucurbitacin B.
    • Echinocystis fabacea - Štětinec laločnatý
  • 23,24-dihydroisocucurbitacin B 3-glukosid
    • Wilbrandia ebracteata [1]:7
  • 23,24-dihydro-3-epi-isocucurbitacin B
    • Bryonia verrucosa
  • Pentanorcucurbitacin B.
  • Kyselina 3,7-dioxo-23,24,25,26,27-pentanorcucurbit-5-en-22-oová
  • cs.wikinew.wiki/wiki/Cucurbitacin#Cucurbitacin_K

Curcumin

  • Anti-angiogenic activity
  • A major ingredient from turmeric,
  • In hepatocyte growth factor (HGF)-treated HUVECs
    • Inhibited cell migration and tube formation via inhibition of PI3K/Akt/mTOR and c-Met/Akt/mTOR signaling
  • Anti-metastatic and anti-angiogenic effects
    • Inhibition of HGF-stimulated tumor growth in the tumor-bearing mouse model
    • Induction of E-cadherin expression
    • Reduction of vimentin, CD34, and VEGF expression
  • Mice inoculated with U87 glioma
    • curcumin suppressed tumor growth by inhibiting VEGF/Ang2/thrombospondin-1(TSP1)-mediated angiogenesis
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Curcumin is the most active curcuminoid in turmeric
  • Anti-invasive effects are partly mediated by
    • Downregulation of matrix metalloproteinase-2 (MMP2)
    • Upregulation of tissue inhibitor of metalloproteinase-1 (TIMP1)
  • Inhibits the transcription of vegf and bfgf
  • Interacts with vegf- and nitric oxide–mediated angiogenesis in tumours
    • Elevated levels of nitric oxide correlate with tumour growth
  • Curcumin reduces nitric oxide generation in endothelial cells
  • Membrane-bound enzyme CD13 (aminopeptidase N) is found in blood vessels undergoing active angiogenesis
    • Curcumin binds to CD13 and blocks its activity
      • Inhibiting angiogenesis and invasion by tumour cells
  • Derivatives of curcumin may be developed to target CD13
    • Providing a novel approach to reduce neoplastic angiogenesis
  • Downregulates the expression of the VEGF and MMP9 genes associated with angiogenesis

Demethoxycurcumin

  • Structural analogue of curcumin isolated from Curcuma aromatica
  • Specifically inhibits the expression of MMP9
  • Curcumin can interfere with the activity of both MMP2 and MMP9
    • Reducing degradation of the ecm
  • Interferes with the release of angiogenic factors that are stored in the ecm
  • Inhibits growth factor receptors such as
    • Egfr and vegf receptor and the intracellular signalling tyrosine kinases
      • This cell signalling system can promote further angiogenesis through gene activation that increases levels of
        • Cyclooxygenase-2 (cox-2)
        • Vegf
        • Il-8,
        • Mmps

A phase i study of curcumin

  • no treatment-related toxicity at doses up to 8000 mg daily
  • Beyond 8000 mg daily, the bulky volume of the drug was unacceptable to the patients
  • Serum concentration of curcumin usually peaked at 1–2 hours after oral intake
    • Gradually declined within 12 hours
  • Study suggested that curcumin may prevent cancer progression
  • Derivatives of curcumin, such as copper chelates of curcuminoids, may have increased antitumour activity
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Cyclo-oxygenase-2 antagonists

  • Ginger
  • Aloe vera
  • Epigallocatechin-3 gallate/green tea
  • Resveratrol
  • Garlic
  • Chinese skullcap
  • Bilberry
  • Grape seed extract proanthocyanidins
  • Panax ginseng
  • Milk thistle
  • Green-lipped mussel
  • Antioxidants (vitamins A, C, E; Se, Zn; carotenoids, flavonoids, coenzyme Q10, N-acetylcysteine, lipoic acid)
  • Boswellia
  • Bromelain
  • Curcumin
  • Quercetin
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/
  • Aspirin, Ibalgin, Voltaren, Meloxicam, ...
  • Kdoule
  • Kurkuma vyšší dávky
  • Nadbytek omega-3 MK - Fish oils: omega-3 fatty acids (eicosapentaenoic acid, docosahexaenoic acid)
    • Antagonizují nevoaskularizaci a aktivitu COX2
  • Lékořice - glycyrrhizic acid and polyphenols
    • Inhibit COX-2, LOX-5, and proteinkinase C (PKC) and also downregulate EGF

Cyclooxygenase inhibitors


Cytogenin - 8-Hydroxy-3-hydroxymethyl-6-methoxyisocoumarin

  • Administration of cytogenin inhibited the production of nitric oxide by macrophages which is known as one of suppressor factors of tumor growth

Daidzein (7,4'- dihydroxyisoflavone), 6,7,4'-trihydroxyisoflavone

Orobol (5,7,3',4'-­tetrahy droxyisoflavone)

  • From fermented soybean
  • Inhibited in vivo angiogenesis in a CAM model by
    • Suppressing VEGF-induced endothelial cell proliferation and expression of Ets1 transcription factor
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Delphinidin

  • A dietary anthocyanidin rich in fruits
  • Suppress bFGF-induced blood vessel formation in the Matrigel plug mouse model
  • In HUVECs, a mechanism study showed that delphinidin inhibited angiogenesis via
    • Deactivating VEGF/ VEGFR-2
      • Followed by inhibiting the ERK1/2 signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Anthocyanidin
  • PH-sensitive, i.e. a natural pH indicator
    • Changes from red in basic solution to blue in acidic solution
  • Primary plant pigment, antioxidant
  • Gives blue hues to flowers in the genera Viola and Delphinium
  • Blue-red color of the grape - Cabernet Sauvignon
  • Cranberries
  • Concord grapes
  • Pomegranates
  • Bilberries

Deoxycorticosterone acetate (DOCA)

  • Aortas harvested from DOCA-treated mice demonstrate evidence of
    • BH4 oxidation,
    • Increased superoxide production
    • Reduced L-arginine to L-citrulline conversion
  • Effects are eNOS-specific and responsive to BH4 treatment [8] or overexpression of GTPCH
  • link.springer.com/article/10.1007/s11897-012-0097-5

Dithioles


Dysoxylum binectariferum (flavopiridol)

Epicatechingallate (ECG)

  • Were also shown to be potent for suppressing tumor angiogenesis when compared to EGCG
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

GC-(4 › 8)-GCG

  • Novel proanthocyanidin extracted from cocoa tea - Camellia ptilophylla
    • A healthy drink in southern China
  • Anti-angiogenic activity in transgenic zebrafish
  • Inhibit the migration and tube formation of HMEC1
    • Decreasing the phosphorylation of ERK, Akt, and p38 MAPK
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

GCH1 polymorphism


Ganoderma lucidum (triterpenoids)

Genistein (5,7,4'-trihydroxyisoflavone)

  • Genistein showed the most potent anti-angiogenic activity
  • Significantly reduced ISVs in transgenic zebrafish
  • Targeted tyrosine phosphorylation of the VEGF SH2 domain to decrease VEGF-mediated endothelial cell proliferation
  • It blocked VEGF and hepatocyte growth factor/scatter factor (HGF/SF)-induced rapid phosphorylation of ERK1/2 and Akt
  • In vivo retinal neovascularization reduced by genistein
    • Due to decreased protein expression of VEGF and HIF1alpha
  • Reduced total neovascularization by significantly lowering CD31 expression
    • Against oral squamous cell carcinoma xenografted in a mice model
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Ginkgo biloba (ginkgolide B)

Ginseng,

  • Also contains anti-angiogenic modulators

Ginsenoside Rk3

  • Anticancer effects of
    • Anti-angiogenic property via the reduction of CD34 in a CAM model

Ginsenosides Rb1

  • Saponin from ginseng
  • Matrigel implant model - ginsenoside Rb1 inhibited angiogenesis and chemo-invasion of endothelial cells
  • Rb1 suppressed the formation of endothelial tube-like structures
    • Via modulation of ERbeta-mediated pigment epithelium-derived factor (PEDF)
  • Blocked angiogenesis by
    • Regulating miR-33a
    • PEDF-mediated activation of the PPARgamma pathway

Ginsenoside Rg3

  • Upregulated mature hsa-miR-520 h (miR-520 h)
    • Decrease the expression of EphB2 and EphB4
      • Inhibiting cell proliferation and tubulogenesis in HUVECs, and SIV formation in zebrafish
  • Rg3 dramatically decreased bFGF-induced angiogenesis in the Matrigel plug animal model
    • By downregulating MMPs such as MMP2 and MMP9
  • Suppressed tumor growth and VEGF-dependent tumor angiogenesis by
    • Attenuating the mobilization of EPCs from the bone marrow microenvironment to the peripheral circulation
  • Anti-angiogenic effect by halting the growth of the ectopic endometrium in rats with endometriosis
    • Blocking the VEGFR2-mediated PI3K/Akt/mTOR signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Ginsenoside Rg3 is abundantly present in Korean Red Ginseng preparation
    • Highly known for its anticancer effects
  • Mostly they amplify the response by stimulating
    • Phosphotidylinositol-4,5-bisphosphate 3-kinase/protein kinase B pathway,
    • Caspase-3/caspase-9-mediated apoptotic pathway,
    • Adenosine monophosphate-activated protein kinase,
    • Nuclear factor kappa-light-chain-enhancer of activated B cells signaling
  • Trigger receptors such as
    • estrogen receptor,
    • Glucocorticoid receptor,
    • N-methyl-d-aspartate receptor
  • www.sciencedirect.com/science/article/pii/S1226845316301427

Glyceollins

  • Soy phytoalexins
  • Significantly suppressed microvessel development and tumor growth
    • Attenuating microvessel and angiogenesis by downregulating
    • VEGF/VEGFR2
    • BFGF/FGFR-1 signaling pathways in vitro
    • Downstream signaling pathways such as
      • ERK1/2, JNK, p38 MAPK, as well as FAK
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Glycyrrhiza glabra (isoliquiritigenin,; glabridin)

Grape seed extract

  • Containing proanthocyanidins
  • Attenuated colon cancer–induced angiogenesis
    • Inhibiting the expression of VEGF and Ang1
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Hesperetin

  • Showed potent anti-angiogenic activities
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Hibiscus sabdariffa L. (protocatechuic acid) - Ibišek

Honey

  • Significantly inhibited IL6-induced neovascularization in a CAM model
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Honokiol and its analogues

  • Can be isolated from Magnolia officinalis
  • Triggered apoptosis via Bax/Bcl-2 and caspase-3-dependent pathway
  • Accompanied by the inhibition of Akt, JAK2/STAT3, and Erk in human oral squamous cells in vitro
  • Honokiol suppressed IL6-mediated migration
  • Reduced the expression of PCNA and CD31
    • Inhibiting the xenograft growth

5-formylhonokiol,

  • Honokiol derivative
  • Significantly inhibited cell invasion, migration, and tube formation in HUVECs in vitro and in zebra fish model in vivo
  • Abolished angiogenesis
    • Inactivating the ERK signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Hyperforin

  • Phloroglucinol derivative from St. John’s wort
  • Acted as a potent anti-angiogenic inhibitor
  • Completely abrogated cell growth, invasion, and tube formation in endothelial cells
    • Complete inhibition of urokinase
    • Significant suppression of MMP2
  • Markedly suppressed tumor growth
    • Associated with its apoptotic induction activity
    • Anti-angiogenic capacity in the expression of CD31
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Indigo Naturalis and its component tryptanthrin

  • Significantly inhibited the in vivo VEGF-induced angiogenesis in a CAM model
  • Tryptanthrin caused cell cycle arrest by dose-dependently decreasing the expressions of
    • Cyclin A,
    • Cyclin B,
    • Cyclin dependent kinase-1 and -2 (CDK1/2)
  • It suppressed cell migration and tube formation in HUVECs
    • Reducing the phosphorylated levels of Akt and FAK
  • Suppress the VEGFR2-mediated ERK1/2 signaling pathway in Matrigel plug mice
  • Reduced the expression of some pro-angiogenic molecules (e.g. Ang1, PDGFB, and MMP2)
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Blue pigment extracted from Assam indigo
  • From the stems and leaves of:
    • Baphicacanthus cusia (Nees) Bremek (family Acanthaceae)
    • Polygonum tinctorium Ait. (family Polygonaceae)
    • Isatis indigotica Fort

Inhibitory of NF-kappa B

.uff.jpg

Inhibiting angiogenesis



Interferon beta

  • Potent inhibitor of angiogenesis by blocking
    • Interleukin-8 (IL-8)
    • Basic fibroblast growth factor (bfgf)
    • Collagenase type v, which are all potent angiogenic factors that aid tumour development and invasiveness
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Isocoumarin

  • Recently discovered angiogenesis inhibitor
  • NM-3 inhibits the proliferation of human umbilical vein endothelial cells in vitro
    • At concentrations 10-fold less than those required to inhibit normal fibroblasts or tumor cells (HT29, MKN28, and MCF-7)
  • NM-3 alone inhibits endothelial sprouting and tube formation in vitro.
  • Synergistic antiproliferative activity with 5-fluorouracil

NM-3 + various chemotherapeutic in tumor xenografts


Isoliquiritigenin

  • From licorice (Glycyrrhiza uralensis Fisch.)
  • Attenuated blood circulation and vascular outgrowth of ISVs in a zebrafish
  • Suppressed the breast cancer growth and neoangiogenesis in breast cancer cells
    • By significantly inhibiting a HIF1alpha/VEGF/VEGFR-2 signaling pathway
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Kahweol

  • A coffee diterpene
  • Confirmed in an ex vivo mouse aortic ring assay, CAM model, and transgenic zebrafish model
  • Anti-angiogenic potential of kahweol attenuates specific angiogenic steps such as
    • Endothelial cell proliferation,
    • Migration, invasion,
    • Tube formation
  • Inhibitory effect on extracellular matrix molecules such as
    • MMP2
    • Urokinase-type plasminogen activator (uPA)
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Livistona chinensis (aqueous extract from seed)

Lycopene

  • A carotenoid pigment rich in tomatoes
  • Significantly reduced the risk of lethal prostate cancer with a lesser degree of angiogenesis
  • Lycopene remarkably inhibited angiogenesis in both the in vitro and in vivo experiments
  • Could inhibit cell migration, invasion, and tube formation in HUVECs
    • Decreased activities of uPA and MMP2
    • Increased protein expression of TIMP2 and PLG activator inhibitor-1
    • Downregulated expression of Rac1.
  • Lycopene attenuated VEGFR2 and its downstream
    • PI3K/Akt and MAPK (ERK and p38 MAPK) signaling pathways
  • Lycopene supplementation attenuated the tumor growth in nude mice xenografted
    • With androgenindependent prostate PC3 tumor
      • Inhibiting cell proliferation via IGF1 signaling
      • Angiogenesis through decreasing VEGF levels in plasma
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]


Lycopene-enriched tomato extract

  • Inhibitory effect on the expression of angiogenic factors
    • VEGF, CD31, HIF1alpha, MMP2, and MMP9
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Magnolia obovata (honokiol)


Magnolia officinalis (Chinese magnolia tree)

Flos magnoliae (magnosalin)


Magnolia seed cones

Matricaria chamomilla (flavonoids: apigenin, fisetin) - Heřmánek


Methotrexate - DHFR inhibition


Accumulation of Methylarginines

  • L-N-monomethylarginine (L-NMMA)
  • Omega-N G,N G-asymmetric dimethylarginine (ADMA)
  • Produced by post-translational methylation of L-arginine residues
  • Liberated by subsequent proteolysis
  • ADMA and L-NMMA may therefore accumulate due to
    • increased methyltransferase activity
    • inhibition of dimethylarginine dimethylaminohydrolase (DDAH)
      • ADMA catabolism
  • Both L-NMMA and ADMA inhibit NOS-mediated NO production
    • By competing with L-arginine to bind at the NOS catalytic site
  • In BH4 depletion
    • L-NMMA increases nNOS-mediated superoxide production
  • Both L-NMMA and ADMA
    • Increase NADPH consumption
    • Superoxide production by eNOS

Minocycline


Mutant Cu/Zn-Superoxide - Amyotrophic Lateral Sclerosis

  • Destabilizes Vascular Endothelial Growth Factor mRNA and Downregulates Its Expression
  • VEGF posttranscriptional processing critically reduces the level of this neuroprotective growth factor and accelerates the neurodegenerative process in ALS.
  • RNA stabilization represents an important posttranscriptional control point for the upregulation of VEGF and other growth factor expression, and may serve as a survival pathway in response to cellular stress (Ross, 1995; Brennan and Steitz, 2001; Guhaniyogi and Brewer, 2001).
  • Hypoxia, inflammatory cytokines, and oxidative stress, for example, all of which have been linked to motor neuron death in ALS (Cleveland and Rothstein, 2001; Ischiropoulos and Beckman, 2003; Shaw, 2005) are strong activators of RNA stabilization.
  • A dysfunction in this pathway may therefore impair the intrinsic defense of a cell against stress.
  • Mutant SOD1 protein destabilizes VEGF mRNA
    • Markedly downregulates protein production.
      • Mediated through the adenylate/uridylate-rich elements (AREs) in the VEGF 3'-untranslated region (UTR), where an aberrant ribonucleoprotein (RNP) complex is formed in the presence of mutant SOD1.
    • “toxic” gain of function of mutant SOD1 that may promote motor neuron death.
  • www.jneurosci.org/content/27/30/7929

NOS Uncoupling

Low BH4 bioavailability relative to NOS or BH2

  • Oxygen activation is “uncoupled” from L-arginine oxidation
  • NOS produces superoxide (O -2 ) instead of NO
  • NOS-derived superoxide reacts with NO to produce peroxynitrite (ONOO-)
    • A highly reactive anion that rapidly oxidizes BH4 and propagates NOS uncoupling
  • BH4 depletion and NOS uncoupling contribute to
    • Overload-induced heart failure
    • Hypertension,
    • Ischemia/reperfusion injury
    • Atrial fibrillation

L-arginine depletion

  • Also promote uncoupling

Methylarginine accumulation

  • Also promote uncoupling

S-glutathionylation of NOS

  • Also promote uncoupling

NaSH


Nobiletin

  • Anti-angiogenic polymethoxylated flavonoid from citrus
  • Concentration-dependent inhibition of VEGF or FGF-induced cell proliferation, migration, and tube formation in HUVECs
  • Nobiletin suppressed production of
    • Pro-MMP2,
    • Expression of MMP2
    • Cellassociated plasminogen activator (PA) activity
    • Expression of urokinase-type PA mRNA
  • Inhibition was associated with the decrease of several signaling factors
    • Erk/2 and JNK
    • Activation of the caspase pathway
  • Nobiletin reduced the formation of intersegmental vessels (ISVs) by
    • Decreasing VEGF-A mRNA expression
    • Inducing G0/G1 phase accumulation in GFP-positive endothelial cells of transgenic zebrafish
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Ocimum sanctum (carnosol, ursolic acid) - bazalka svatá

Oleanolic acid

  • Olive oil,
  • Phytolacca americana (American pokeweed),
  • Syzygium spp,
  • Garlic, etc.
  • Olea europaea (leaves, fruit),
  • Rosa woodsii (leaves),
  • Prosopis glandulosa (leaves and twigs),
  • Phoradendron juniperinum (whole plant),
  • Syzygium claviflorum (leaves),
  • Hyptis capitata (whole plant),
  • Mirabilis jalapa
  • Ternstroemia gymnanthera (aerial part)
  • Java apple (Syzygium samarangense) and rose apples
  • Ocimum tenuiflorum (holy basil)
  • en.wikipedia.org/wiki/Oleanolic_acid

Oleuropein

  • Non-toxic olive iridoid
  • Anti-tumor agent
  • Derived from the olive tree
  • Powerful antioxidant and anti-angiogenic agent

Omega-3 fatty acids (eicosapentaenoic acid, docosahexaenoic acid)


Panax ginseng (saponins: 20(R)- and 20(S)-ginsenoside-Rg3)


Panduratin A (PA)

  • Natural chalcone isolated from Boesenbergia rotunda (L.) Mansf.
  • Suppressed VEGF-induced cell survival
  • Supressed proliferation, migration, invasion, morphogenesis, and tube formation in HUVECs
  • Inhibited neo-vessels formation in a Matrigel plug mice model and zebrafish embryos
  • Prevented cell migration via
    • Suppressing MMP2 activation and F-actin stress fiber formation
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Passiflora caerulea

  • Significantly inhibited IL6-induced neovascularization in a CAM model
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Passiflora incarnata

  • Significantly inhibited IL6-induced neovascularization in a CAM model
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Pleurotus tuber-regium (Fries) Singer (PTR)

  • An edible medicinal mushroom
  • Ethanol extract from the sclerotium containing
    • Protocatechuic, chlorogenic, syringic, and folic acids
  • Can inhibit endothelial cell migration and tube formation
    • By downregulating gene expression of:
      • VEGF, VEGFR, FGF, ANG-Tie, and MMPs
  • Prevented the formation of sprouts in SIVs in zebrafish embryos in vivo
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Polygonum cuspidatum (Japanese knotweed)


Polygonum cuspidatum (resveratrol)


Polygonum cuspidatum Whole plant

Polypodium leucotomos (difur)


Poria cocos (1–3-beta-d-glucan)


Poria cocos

Propolis

  • Significantly inhibited IL6-induced neovascularization in a CAM model
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Quercetin

  • Ubiquitous flavonoid present at high levels in vegetables and beverages
  • Can inhibit angiogenesis
  • Exhibited significant inhibition on cell proliferation, migration, invasion, and tube formation in HUVECs via:
    • Suppression of VEGF/VEGFR2 signaling transduction
    • Downstream protein kinases
    • Including AKT,
      • Mammalian target of rapamycin (mTOR),
    • Ribosomal protein S6 kinase, and ERK
  • The anti-angiogenic effect of quercetin suppressed tumor growth in various tumor-bearing mice models
It reduced angiogenesis by decreasing
    • VEGFA,
    • Cyclooxygenase-2 (COX2)
    • INOS and NO levels
  • By decreasing serum VEGF, and reducing microvessel density in tumor tissues
    • Via a calcineurin/NFAT pathway with reduced protein levels of VEGF, VEGFR2, and NFATc3
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Quercetin-4'-O-beta-D-glucopyranoside

  • Derived constituent of onion peel
  • Attenuated angiogenesis by suppressing VEGFR2 in zebrafish and endothelial cells via:
    • Inhibition of VEGFR2-mediated signaling transduction,
      • Followed by deactivation of c-Src, FAK, ERK, AKT, mTOR, and S6K
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Rabdosia rubescens Hora (ponicidin and oridonin)


Rabdosia rubescens hora (Rabdosia)


Radix Salvia Miltiorrhiza

  • Lipid-soluble components isolated from
  • Several tanshinones have anti-angiogenic properties.

Tanshinone IIA (TanIIA)

  • The most abundant tanshinone in this herb
  • Confirmed in a CAM model
  • Attenuated cell proliferation, migration, invasion, and tube formation in HUVECs in vitro
    • Inhibition of VEGF/VEGFR2, CD146 (melanoma adhesion molecule), MMP2/TIMP2, and MMP9 in HUVECs in vitro
  • Human aortic smooth muscle cells, TanIIA blocked matrix invasion through
    • AKT-mediated IkappaBalpha phosphorylation
    • P65 nuclear translocation,
    • Tumor necrosis factor-alpha (TNFalpha)-induced ERK
    • C-jun phosphorylation
    • NFkappaB
    • AP1 DNA binding
  • TanIIA also interrupted a HIF1alpha/beta-catenin/TCF3/LEF1 signaling pathway
    • In the hypoxic microenvironment of the xenografts of human colorectal cancer in a nude mice model
  • Human breast cancer xenografts of nude mice, TanIIA suppressed HIF1alpha and VEGF
    • Correlated with
      • Deactivation of mTOR’s effectors ribosomal protein S6 kinase (p70S6K)
      • Eukaryotic initiation factor 4E-binding protein-1 (4E- BP1)

Tanshinone I (TanI)

  • Significantly attenuated VEGF-induced cell proliferation, migration, invasion, and tube formation in HUVECs and neovascularization in a CAM model.
  • TanI suppressed tumor angiogenesis by reducing the phosphorylation of Stat3 and hypoxia-induced HIF1alpha accumulation
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Cryptotanshinone

  • Significantly attenuated VEGF-induced cell proliferation, migration, invasion, and tube formation in HUVECs and neovascularization in a CAM model.
  • Cryptotanshinone reduced VEGF-induced angiogenesis
    • Through inhibiting the phosphorylation of VEGFR2 and its key downstream kinases, including ERK1/2, p90RSK, Src, and FAK
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Resveratrol

  • Phytoalexin found in grapes and wine
  • Anti-angiogenic activity
  • Inhibit division in huvecs and to decrease the lytic activity of mmp-2
  • Inhibits vegf-induced angiogenesis
    • By disruption of reactive oxygen species–dependent src kinase activation
      • Subsequent ve-cadherin tyrosine phosphorylation
  • Resveratrol inhibits the growth of gliomas in rats by suppressing angiogenesis
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Rosmarinus officinalis (carnosol and ursolic acid)


Drugs containing dithiolethione moieties (S-NSAIDs)


S-valproate


Scrophularia ningpoensis Root


Scutellaria baicalensis - Šišák bajkalský - Chinese skullcap herb.

Scutellarein, scutellarein tetramethyl ether

  • Showed potent anti-angiogenic activities
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]
  • Baicalin and baicalein
  • Main derivatives
  • Potent anti-angiogenic compounds that reduce
    • Vegf, bfgf,
    • 12-lipoxygenase activity,
    • Mmp 90
  • Clinically active against advanced prostate cancer
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Selenium

Shark cartilage (water soluble extract AE-941)

Shikonin

  • Derived from Lithospermum erythrorhizon
  • Can suppress cell proliferation, migration, and network formation in HUVECs
    • Decreased expression of ITGAVbeta3
  • Reduced TNFalpha-induced and B16 melanoma–induced angiogenesis in the mice and CAM model
  • Attenuated tumor growth in a xenograft model
    • Causing cell cycle arrest in HCT116 cells
    • Decreased the activity of hypoxia-induced HIF1alpha and its downstream mTOR/p70S6K/4E-BP1/eIF4E signaling pathway

Beta-hydroxyisovalerylshikonin (beta-HIVS)

  • Inhibited angiogenesis in a CAM model
  • More efficient than shikonin
  • Suppressed angiogenesis via inhibition of VEGFR2 and Tie2 in endothelial cells
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]


Silybum marianum (silymarin)

Silybum marianum (milk thistle)


Sinensetin

  • Showed potent anti-angiogenic activities
  • Polymethoxylated flavonoid from citrus
  • Possessed the strongest anti-angiogenic property by
    • Inducing cell cycle arrest at the G0/G1 phase in HUVECs
    • Decreasing mRNA expression of flt1, kdr, and hras in zebrafish
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Skořice


Squalus acanthias (dogfish liver: squalamine)

  • Squalus acanthias (Dogfish Shark)
  • Cationic steroid isolated from the liver of the dogfish shark, Squalus acanthias
  • Squalamine significantly blocks vegf-induced activation of mitogen-activated protein kinase and cell proliferation in human vascular endothelial cells
  • Anti-angiogenic for ovarian cancer xenografts
  • Appears to enhance the cytotoxic effects of cisplatin chemotherapy
    • Independent of HER2 status
  • Overexpression of HER2 is normally associated with resistance to cisplatin and promotion of tumour angiogenesis

Phase ii trial of patients with advanced small-cell lung cancer

  • Squalamine 300 mg/m2 by continuous infusion for 5 days, with paclitaxel and carboplatin given on day 1
  • Survival data and a satisfactory safety profile indicated that the combination should be explored further
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Stilbene glycosides from the medicinal plant Boswellia papyriferai

  • Trans-4',5'-dihydroxy-3-methoxystilbene-5-O-{alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->6)}-beta-D-glucopyranoside
  • Inhibited FGF-2-induced proliferation, wound healing, invasion in Matrigel, tube formation and angiogenesis in large and small vessel-derived endothelial cells and also in the chick chorioallantoic membrane assay
  • Reduced binding of FGF-2 to fibroblast growth factor receptors-1 and -2
  • pubmed.ncbi.nlm.nih.gov/19389252/

Sulforaphane

  • From cruciferous vegetables
    • Broccoli
    • Cabbages
  • Markedly suppressed tumor growth of HepG2 cells in a CAM model by downregulated
    • Expression of HIF1alpha
    • VEGF in tumors
  • In HUVECs, sulforaphane exerted anti-angiogenesis effects by
    • Reducing HepG2 cell-stimulated cell migration, adhesion, and tube formation
  • The inhibition of STAT3/HIF1alpha/VEGF signaling
    • Associated to sulforaphane’s anti-angiogenic effect against hepatocellular carcinoma in HepG2 cells
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Tanacetum parthenium L. (parthenolide)


Taxus brevifolia (Pacific yew)


Taxus brevifolia (taxoids)


Taxus chinensis Bark

Theaflavin-3,3'-digallate (TF3)

  • Inhibited human ovarian carcinoma-induced angiogenesis in HUVECs and in a CAM model by
    • Downregulating the activation of the Akt/mTOR/p70S6K/4E-BP1 pathway
      • Akt/c-Myc pathway
  • Also inhibited cancer cellinduced angiogenesis by
    • Reducing the cleavage of Notch-1 and expression of c-Myc, HIF1alpha, and VEGF
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Tricin (4',5,7-trihydroxy-3',5'- dimethoxyflavone)

  • One of the rice bran constituents
  • Significant anti-angiogenic effect in a CAM model
  • Inhibited VEGF-induced cell proliferation, invasion, and tube formation in HUVECs.
  • Suppressed tumor cell–induced angiogenesis
    • By downregulating
      • HIF1alpha-enhanced VEGF expression in tumor cells
      • Reactive oxygen species (ROS)-mediated VEGFR2 signaling pathway in endothelial cells
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Viscum album (European mistletoe)

Viscum album (lectins)

  • Herbs and their derivatives that specifically inhibit vascular endothelial growth factor and have direct activity against angiogenesis
  • Viscum album (European mistletoe) Contains mistletoe lectin iii (ML3A)
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Viscum album (lectins)Viscum album (European mistletoe) Iscador (Weleda, Palisades, NY, U.S.A.)

  • Herbs and their derivatives that specifically inhibit vascular endothelial growth factor and have direct activity against angiogenesis
  • Contains mistletoe lectin iii (ML3A)
  • Often used as an anticancer agent in anthroposophic and homeopathic medicine
  • Anti-angiogenic by downregulation of vegf
  • Induces apoptosis of cancer cells
  • Increase in survival in a variety of cancers
  • www.ncbi.nlm.nih.gov/pmc/articles/PMC1891166/

Vitamin D (1alpha,25-D3)

Vitis vinifera (grape seed extract) Contains 95% proanthocyanidins

















Zerumin A

  • Mainly accumulates in the fruits of Alpinia caerulea (R.Br.) Bentham
    • A flavoring spice and a ginger substitute
  • Identified as an anti-angiogenic agent
  • Zerumin A could dose-dependently inhibit vessel formation in a transgenic zebrafish model
    • Via inh. VEGFA, KDR, ANG1, ANG2, Tie1, and Tie2
  • Inhibited cell proliferation and migration in HUVECs to prevent angiogenesis.
  • [Pro-Angiogenic and Anti-Angiogenic Effects of Small Molecules from Natural Products; Jing-Yi MaXuelin Zhou]

Zingiber officinale (6-gingerol)

Zingiber officinalis (ginger)

Interferon-gamma blocks signalling through PDGFRß in human brain pericytes

Angiogenesis inhibitors

Angiogenesis inhibitors

Bevacizumab, sevacizumab, apatinib, cediranib, pazopanib, tivozanib, and VB-111

  • Can induce hypoxia-inducible factor (HIF-1A)
    • Subsequently causes upregulated VEGF production and increased CSCs
    • Therefore, a combination of anti-angiogenic drugs and CSC-targeted therapies may provide promising treatment options

Ligusticum wallichii

  • Dried rhizome of Umbelliferae chuanxiong
  • Relieving pain
  • Can inhibit the expression of VEGF, HIF-1alpha and EMT-related proteins in stem-like cells
  • Can also inhibit the primary tumor model and recurrence model of lung cancer stem cell-like tumor-bearing mice
    • Related to the inhibition of HIF-1alpha and EMT-related molecule expression
  • Improve the hypoxic microenvironment of tumor
    • By inhibiting HIF-1alpha expression
      • Had a inhibit ing effect on CSC
  • May also inhibit CSC by inhibiting the mRNA expression of EMT-related marker proteins at the mRNA level
  • www.oatext.com/chinese-herb-in-the-treatment-and-regulation-of-cancer-stem-cells.php

Soy isoflavones (genistein, daidzein)

Tanshinone IIA (Tan-IIA)

  • Diterpenoid quinone ingredient extracted from the Chinese Herb salvia miltiorrhiza
  • Neuroprotective, anti-inflammatory, anti-tumor and other
  • Promoting tumor cell apoptosis,
  • reversing tumor multi-drug resistance
  • inhibiting angiogenesis and metastasis
  • Tan-IIA can targets and inhibits CSC, and through the block IL - 6/STAT3/NF-kB signaling pathways
    • In inhibiting the growth of human breast CSC in vivo and in vitro
  • Inhibition of proliferation, less stemness
  • Induction of apoptosis and targeted and inhibit the CSC
  • High dose of Tan-IIA can promote apoptosis of PG stem cell-like cells
    • Its ability to promote apoptosis
  • Pro-apoptotic capacity is equal to or greater than that of cisplatin
  • After Tan-IIA treatment
    • The adhesion, invasion and chemotaxis ability of gastric cancer MKN-45 cells were significantly inhibited
    • Heterogeneous adhesion molecule CD44V6 was decreased,
    • Expression of E-acdherin was up-regulated
    • Ability of tumor cells to penetrate the extracellular matrix and basement membrane was decreased
  • Tan-IIA can also inhibit the migration and invasion of cervical cancer stem cell-like cells
    • By inhibiting the transcriptional activity of YAP
  • www.oatext.com/chinese-herb-in-the-treatment-and-regulation-of-cancer-stem-cells.php

Valproic acid

Xiaotan Sanjie Formula

Pinellia, Nanxing, Ji Nei Jin, Chen Pei, etc.,

  • May down-regulate the expression of Notch-1 and Hes1 genes
  • Reduce tumor angiogenesis
  • Inhibit the proliferation of gastric cancer stem cells in a dose-dependent manner
  • Enhance the expression of apoptotic protein Bax,
  • Inhibit of apoptotic protein Bcl-2 expression decreased
  • Dose-dependent induce the apoptosis of colon cancer stem cell-like cells
  • Reducing the expression of PCNA in gastric cancer cells
    • Can inhibit the proliferation activity of gastric cancer cells
    • Reduce the heterogeneous adhesion by affecting the expression of adhesion molecules CD44 and CEA of gastric cancer cells
  • www.oatext.com/chinese-herb-in-the-treatment-and-regulation-of-cancer-stem-cells.php


O úroveň výše

Poslední aktualizace: 10. 12. 2023 20:34:38