The list below is copied from a paper published last year [1].
As many might recall, untreated tumors outgrow their blood supply. Contrary to popular belief, cancer does not "hate" oxygen. Oxygen insufficiency (hypoxia) results in production of HIF-1alpha (hypoxia-inducible factor-1alpha), which triggers the appearance of VEGF (vascular endothelial growth factor). The purpose of VEGF is to promote the construction of new blood vessels to feed the growing needs of the tumor.
HIF-1alpha has many other functions, all related to cell survival. It is therefore not a surprise that HIF is at the root of treatment resistance.
Paradoxically, although it would seem good to starve PCa, it is better to forestall the appearance of HIF by improving the blood supply, e.g. via nitroglycerine,
An additional approach is to inhibit VEGF. Drugs that do this have serious downsides.
Supplements that affect VEGF are considered to be safe at normal dietary levels. I have no idea as to the safety & effectiveness of the following at much higher doses or in combination.
It's a long list & needs some annotation. e.g.
"Delphinidin Punica granatum is a member of the Lythraceae family. Its fruit is famous worldwide owing to its nutraceutical and functional benefits."
Why so coy? The 'famous' fruit is the pomegranate.
"The most abundant phytochemicals in pomegranate juice are polyphenols, including the hydrolyzable tannins called ellagitannins formed when ellagic acid and gallic acid bind with a carbohydrate to form pomegranate ellagitannins, also known as punicalagins. The red color of the juice is attributed to anthocyanins, such as delphinidin, cyanidin, and pelargonidin glycosides." [2]
The List.
"3.2. Regulation of VEGF and Its Related Factors by Phytochemicals
3.2.1. Flavonoids
Amentoflavone
Amentoflavone is a bioactive bioflavonoid present in Chrozophora senegalensis. It inhibits VEGF expression by interacting with and inhibiting the production and activation of transcription factor-2, cyclic adenosine monophosphate response binding protein, TNF-α, IL-1β, IL-6, and NF-kB to prevent the metastasis of and angiogenesis in human breast cancer [82,83]. It also interacts with VEGF and inhibits its expression by preventing the phosphorylation of VEGFR1 and VEGFR2. Furthermore, it inhibits endothelial cell migration induced by VEGFA and PLGF-1 [84]. This indicates that C. senegalensis can be a useful source of bioactive constituents that provide protection against cancer.
Baicalein
Scutellaria baicalensis is a flowering plant belonging to the Lamiaceae family. Baicalein, a flavone derivative isolated from this plant, suppresses CD45 expression and pulmonary metastasis. It markedly reduces lung cancer cell proliferation and cancer growth, as well as prolongs cell survival. In addition, it suppresses the protein expression of VEGF and 12-lipoxygenase. Moreover, it reduces microvessel density, the mitotic index, and VEGF and FGFR2 expression, as well as increases RB-1 expression [85]. A recent study revealed that it exhibits an anti-angiogenic effect by reducing the activator protein-1expression (AP-1), promoting AP-1 degradation, and weakening the MMP2/9 expression in relation to VEGF in an inflammation microenvironment [86].
Delphinidin
Punica granatum is a member of the Lythraceae family. Its fruit is famous worldwide owing to its nutraceutical and functional benefits. Delphinidin is an anthocyanidin found in P. granatum and it exhibits potential pharmacological activities, including antitumor, anti-mutagenic, anti-inflammatory, and antioxidant activities. In lung cancer cells, it exerts anti-angiogenesis activity by suppressing CoCl2- and EGF-induced VEGF protein production, mRNA expression, HIF-1α expression, and HRE promoter activity [78].
Kumatakenin
Syzygium aromaticum is a member of the Myrtaceae family. The flower bud of this plant has a long history of use as a herbal medicine and spice. Kumatakenin, an O-methylated flavonol anticancer agent isolated from this plant, inhibits ovarian cancer by suppressing MCP-1 and RANTES expression. In addition, it inhibits the cancer-promoting factors, including VEGF, MMP9, MMP2, and IL-10, in macrophages stimulated by ovarian cancer cells [87].
Licoricidin
Glycyrrhiza uralensis is a member of the Fabaceae family. Licoricidin, an isoflavone-type ingredient of this plant, exhibits an anticancer effect by suppressing the expression of VEGFA, COX-2, iNOS, HIF-1α, CD31, CD45, lyve-1, VEGFR2, VEGFR3, VEGFRC, VCAM-1, ICAM, and MMP9 [88].
Luteolin
Arachis hypogaea is a member of the Fabaceae family. Its seed oil exhibits pectoral, emollient, demulcent, and aperient effects, and it is consumed mainly as a nutritive food. In folk medicine, it is known to exert aphrodisiac and anti-inflammatory activities. Luteolin, a bioactive flavone derivative present mainly in its shell, exerts anticancer activities. It provides effects against breast cancer through anti-angiogenesis mechanism by inhibiting VEGF production and its binding with the receptor. In addition, it also downregulates epithelial–mesenchymal transition markers and lowers metastatic activity. Furthermore, it suppresses apoptosis and receptor tyrosine kinase activity, as well as prevents incipient colonization of breast cancer [89]. Recent studies have revealed that it inhibits vasculogenic mimicry formation and angiogenesis through inhibiting VEGF expression dependent on Notch 1 expression [90].
Oroxin B
Oroxylum indicum is a flowering plant belonging to the Bignoniaceae family. Traditionally, this plant is used as food, a traditional medicine, and part of marriage rituals. Oroxin B, a flavone glycoside isolated from this plant, suppresses proliferation of liver cancer cells. Furthermore, it suppresses COX-2/VEGF and PTEN/PI3K/Akt signaling pathways [91].
Quercetin
Fagopyrum esculentum is a member of the Polygonaceae family and popularly used in a cooked form for treating anemic patients. Quercetin, a plant flavonol, is contained in many plants, including onions, broccoli, raspberries, apples, citrus, Nelumbo nucifera, and leafy greens. It inhibits VEGF expression via multiple signaling pathways, including interaction with NF-kB nuclear transcription protein and hypoxia. Another study investigated the interaction of quercetin with PlGF-1 and VEGFA, but no interaction was found [84]. Other studies have shown that it reduces tumor weight by targeting VEGFR2 through the Akt/mTOR/P70S6K signaling pathway [92,93]. These findings indicate that edible or medicinal plants containing quercetin can be helpful in fighting cancer.
Scutellarein
Scutellaria lateriflora belongs to the Lamiaceae mint family, and it is employed as a mild sedative and sleep promoter. Scutellarein, a flavone present in S. lateriflora, reduces oxidative stress and suppresses the development of lymphoma and liver cancer. It also suppresses the expression of MMP2, MMP9, HIF-1α, Flt-1, and VEGFA. It also induces apoptosis by promoting caspase-3 DFF-40-controlled nucleosomal degradation [94,95,96].
Wogonin
Scutellaria baicalensis belongs to the Lamiaceae family and has been used over the years in traditional Chinese medicine to cure and treat respiratory infection, inflammation, insomnia, hemorrhage, hypertension, dysentery, and diarrhea. Wogonin, an O-methylated flavone found in this plant, suppresses cell proliferation, G0/G1 sub-population, and cell invasion. It downregulates the expression of ER-α, VEGF, Akt, and Bcl2, upregulates the expression of p53 and Bax, increases caspase-3 cleavage, and promotes apoptosis [96,97].
3.2.2. Phenol, Polyphenol, and Phenolic Acid Derivatives
Arctigenin
Arctium lappa, also known as greater burdock, belongs to the Asteraceae family. It is cultivated in gardens to be used as a vegetable. In folk medicine, its dried root is known to exhibit blood-purifying, diaphoretic, and diuretic properties. It is an important ingredient of Essiac tea, which is used for cancer recovery. Arctigenin, an active lignin constituent of this plant, exerts an anti-inflammatory property and has the potency to cure prostate cancer by downregulating the expression of VEGF, EGF, and bFGF, as well as upregulating the expression of Bax/Bcl-2 [98].
Catapol
Rehmannia glutinosa is a species in the Orobanchaceae family. Traditionally, it has been used to cure diabetes, uterine bleeding, and urinary incontinence, as well as to regulate menstrual flow. Catapol, an iridoid glucoside isolated from this plant, shows several pharmacological activities, including antitumor, anti-inflammatory, and antiapoptotic activities. It ameliorates cancer in colon tissue by inhibiting the expression of VEGF, VEGFR2, HIF-1α/b, FGF, IL-1β, -6, -8, COX-2, and iNOS [99].
Curcumin
Curcuma longa is classified as a member of the Zingiberaceae family. In many Asian cuisines, it is considered to be a key ingredient. Usually, C. longa is used in the form of rhizome powder. Curcumin, a diarylheptanoid of the dried rhizome of C. longa, has been considered to possess an anticancer effect. It suppresses gastric carcinoma proliferation by inducing apoptosis in tumor cells, activating immune cells to release cytokines, and suppressing the STAT3, VEGF, HIF-1α, and DEC1 signaling transduction pathways [100].
Garcinol
Garcinia indica is a member of the Clusiaceae family and has been used for industrial, pharmaceutical, and culinary purposes. Garcinol, a polyisoprenylated benzophenone isolated from G. indica fruit, can potentially inhibit the growth and proliferation of oral cancer cells by inhibiting the expression of COX-2 and NF-kB to promote apoptosis [101].
Neoalbaconol
Albatrellus confluens belongs to the Albatrellaceae family. Neoalbaconol, an active constituent isolated from this plant, suppresses VEGF-induced proliferation, migration, invasion, and capillary-like tube formation of human umbilical vascular endothelial cells (HUVECs). Moreover, it inhibits the activation of the VEGF receptor and downregulates the related signaling pathway. It blocks EGFR-controlled VEGF formation and inhibits cancer angiogenesis in breast cancer [102].
Oxyresveratrol
Oxyresveratrol, a polyhydroxylated stilbene, is present in a large amount in Morus alba, and it has notably been employed as a herbal medicine. It inhibits cancer growth and metastasis, microvessel density, and micro-lymphatic vessel density. In addition, it also inhibits VEGFR-3, VEGFC, and CD31, and provides protection against cancer growth [103].
Resveratrol
Polygonum cuspidatum is a member of the Polygonaceae family. Resveratrol, an active stilbene ingredient of this plant, is comprised of various pharmacological activities, including anticancer activity. Resveratrol and its derivative, acetyl resveratrol, suppress the cell growth metabolism of SKOV-3 aggregates. The inhibition of cell growth interlinks with the attenuation of VEGF secretion and NF-kB protein levels [104].
Rosmarinic Acid
Rosmarinic acid is a water-soluble phenolic compound present in many medicinal plants, such as Salviae miltiorrhizae and Rosmarinus officinalis. It inhibits VEGF expression by inhibiting the production of IL-8 [105]. A recent study has shown that rosmarinic acid prevents the secretion of VEGF, IL-6, TGF-β, TNF-α, and NF-kB in H22 tumor-bearing mice, proving its potential as an antitumor agent [106]. Rosmarinic acid was indicated to prevent cancer by inhibiting inflammation and angiogenesis mechanisms.
3.2.3. Terpenoids, Steroids, Lignans, and Fatty Acids
3-O-acetyloleanolic Acid
Vigna sinensis is an herbaceous legume in the Fabaceae family. 3-O-acetyloleanolic acid, a pentacyclic triterpenoid compound present in this plant, has the potency to inhibit angiogenesis and cancer. It reduces the expression of VEGFA, suppresses the expression of VEGFR1 and VEGFR2 and the phosphorylation of PI3K, FAK, Akt, and ERK1/2, and inhibits cancer-promoted lymphogenesis and sentinel lymph node metastasis [107].
Actin
Cimicifuga foetida is a member of the Ranunculaceae family. It notably blocks cancer growth by suppressing cancer cell proliferation and reducing the migration and motility of cancer cells. Its mechanism involves the suppression of the VEGFR1, pERK, pINK, and JNK/ERK pathways. In addition, in breast cancer, it downregulates the expression of VEGFR1 and CXCR4 [108].
Ginsenoside Rg3
Panax ginseng belongs to the Araliaceae family. Ginsenoside Rg3, an active triterpenoid saponin, exerts an antiangiogenic effect by downregulating the VEGF/P38/ERK signaling pathway and inhibits the tube formation and migration of progenitor cells. It inhibits ectopic endometrium growth by suppressing the VEGFR-controlled PI3K/Akt/mTOR signaling pathway, exhibiting its anti-angiogenesis and proapoptotic effects [109].
Artemisinin
Artemisinin, a sesquiterpene, is a well-known antimalarial agent extracted from Artemisia annua. A recent study proved that artemisinin could be used as an anticancer agent. It prevents cancer by regulating multiple pathways. It decreases the expression level of VEGF, NF-kB, VEGF-Flt-1, and KDR/Flk-1 receptors in endothelial cells, thereby promoting anticancer activity [110].
Artesunate
Artesunate is a semisynthetic derivative of artemisinin. It prevents cancer development by inhibiting angiogenesis in a dose-dependent manner in HUVECs. It reduces immunosuppression and provides anticancer immunity to fight cancer by reducing the level of TGF-β1 and IL-10 [111]. This indicates that artesunate can be a significant anticancer agent.
Astragaloside IV
Astragalus membranaceus is a member of the Leguminosae family, and its dried root is a folk remedy used to repair and regenerate injured tissues and organs. Moreover, it helps to relieve stress and stress-related diseases. Astragaloside IV, a major constituent of this plant, suppresses cancer cell proliferation and terminates tumor development. It has been indicated to downregulate the PCNA, Ki67, MMP2 and 9, and VEGF signaling pathways. In addition, it potentially inhibits the MAPK/ERK signaling pathway [112].
Capsicodendrin
Cinnamosma macrocarpa is a member of the Canellaceae family, and its major active dimeric drimane-type sesquiterpene is capsicodendrin. Capsicodendrin inhibits VEGFR2, downregulates Akt, and induces autophagy by increasing LC3 cleavage and expression of autophagy-related genes (Atg3), Atg5, and beclin 1. Capsicodendrin-mediated reductions in sub-intestinal vessel formation and intersegmental vessel sprouting suppress sprouting angiogenesis and, ultimately, cancer growth [113]. It inhibits the phosphorylation of VEGFR2, eNOS, and Akt to regulate endothelial progenitor cells.
Celastrol
Tripterygium wilfordii belongs to the Celastraceae family and has traditionally been used to cure psoriasis and rheumatoid arthritis. Celastrol, a triterpene bioactive constituent, has been shown to exhibit an antitumor cancer effect by reducing the proliferation and migration of prostate cancer cells [114]. In addition, it suppresses the expression of VEGF and TNF-α.
Eriocalyxin B
Isodon eriocalyx is a member of the Lamiaceae family, and it exerts several potential biological activities. Eriocalyxin B, an active diterpenoid isolated from this plant, exerts its anticancer activity by suppressing VEGF-promoted cell proliferation, tube formation, cell migration, and cell invasion. In addition, it promotes G1-phase cell cycle arrest, which is interlinked with suppression of CDK4 and cyclin D1, and ultimately blocks the expression of phosphorylated retinoblastoma protein. Furthermore, it interacts with ATP-binding sites and suppresses VEGF-promoted phosphorylation of VEGF receptor-2, exhibiting its anti-angiogenesis activity to cure cancer [115].
Ginsenoside Rd
P. ginseng is an important plant that grows in China, Korea, and Siberia. The root of this plant is valuable and orally consumed to improve Alzheimer’s disease, memory, concentration, thinking power, muscle damage, physical stamina, and work efficiency. Ginsenoside Rd, a potent triterpenoid ingredient of this plant, suppresses VEGF-induced migration, proliferation, and tube formation of HUVECs. In addition, it ameliorates VEGF-promoted sprouting of vessels and suppresses vascular formation. In human breast cancer cells, it also exerts an angiogenic effect with a potential anticancer effect [116].
Ilexgenin A
Ilex hainanensis is a member of the Aquifoliaceae family and a traditional remedy for curing inflammation, dyslipidemia, and hypertension. Ilexgenin A, its novel, active pentacyclic triterpenoid component, exerts antitumor activity and promotes cell cycle arrest. In HepG2 cells, it suppresses the inflammatory cytokines IL-6 and TNF-α, inhibits VEGF production and transcription, and inhibits the PA3K and STAT3 signaling pathways [117].
Lupeol
Senegalia visco is a perennial tree belonging to the family Fabaceae. Lupeol, a phytosterol, is a major constituent present in this plant and it suppresses the migration, viability, and morphogenesis of HUVECs. It also lowers TNF-α transcription, downregulates VEGFR2 signaling, and phosphorylates FAK, PCL, Akt, and Src. In addition, it also interferes with cancer angiogenesis and suppresses cancer growth [118].
Oridonin
Rabdosia rubescens is an herbaceous plant belonging to the Labiatae family. Traditionally, it has been used to treat prostate cancer. Oridonin, a terpene compound isolated from R. rubescens, is employed as a therapeutic drug and dietary supplement. Pharmacologically, it exerts anticancer activity, suppresses HUVEC proliferation, migration, invasion, and tube formation, and induces cell apoptosis. Furthermore, it downregulates VEGFA, VAGFR2, and VEGFR3 expression, and upregulates TP53 expression. With these mechanisms, it inhibits cancer growth and metastasis [119].
Pomolic Acid
Euscaphis japonica belongs to the Staphyleaceae family. Its fruit is used as a drug. This plant contains an active triterpenoid, named pomolic acid, that suppresses cancer cell proliferation. The mechanism of this effect in MCF-7 and HUVEC cells involves the suppression of EGF-promoted VEGF/HIF-1α expression. In addition, pomolic acid downregulates EGF-promoted p38-MAPK phosphorylation and mTOR [120].
Stigmasterol
Gundelia tournefortii, a member of the Asteraceae family, is famous for its valuable health benefits for diabetes, intestinal diseases, cancer, and epilepsy. Stigmasterol, an abundant phytosterol isolated from this plant, exhibits potential anticancer properties through the VEGF signaling pathway [121]. Stigmasterol inhibits angiogenesis through the VEGF signaling network. It reduces the phosphorylation form of FAK, PCL, SRC, and VEGFR2 and inhibits endothelial cell proliferation and migration as well as well capillary network formation through disruption of the TNF–VEGFR2 axis [122].
Tanshinone IIA
Salvia miltiorrhiza belongs to the Lamiaceae family. It is famous for the use of its root in traditional Chinese medicine. Tanshinone IIA, a major, bioactive diterpene quinone compound present in this plant, controls the angiogenesis functions in HUVECs and inhibits VEGF-induced migration and tube formation of human progenitor cells (EPCs) without causing cellular toxicity. A detailed mechanism study indicated that the PLC, Akt, and JNK signaling pathways are involved in controlling angiogenesis [123].
Thymoquinone
Nigella sativa is a flowering plant belonging to the Ranunculaceae family. Thymoquinone, a major monoterpene isolated from this plant, has exhibited effects against several different types of cancers in a number of preclinical studies. It attenuates tumorigenic signaling, including those controlled by EGF, FGF, VEGF, TGF-β, and various metastatic, angiogenic, and pro-mitogenic factors [124].
3.2.4. Coumarins
Daphnetin
Daphne odora is a member of the Thymelaeaceae family. The stems and flowers exert several biological activities, including ophthalmic, depurative, anti-spasmodic, antiphlogistic, and anodyne activities. Daphnetin, a bioactive constituent of this plant, has been shown to exert different pharmacological effects, such as anti-inflammatory, anti-arthritic, and antitumor effects. It inhibits angiogenesis induced by TNF-α and VEGF by downregulating the IKKS/IkBα/NF-kB, Src/Fak/ERK1/2, and Akt signaling pathways. Taken together, the potential of daphnetin as a multi-target anticancer agent has been shown [125].
Esculetin
The root of Cichorium intybus, a member of the Asteraceae family, is used to protect against dropsy and liver and spleen diseases. Esculetin, a coumarin derivative, inhibits VEGF-induced proliferation and DNA synthesis, as well as downregulates MMP9 expression in HUVECs. Furthermore, esculetin reduces VEGFR2 phosphorylation and downregulates the ERK1/2 and eNOS/Akt signaling pathways, showing its potential role in inhibiting cancer progression [126].
Scopoletin
Nicotiana glauca is a member of the Solanaceae family. The leaves of this plant are used in hunting rituals by the Cahuilla Indians. Moreover, the leaves are also used to treat swollen glands, an inflamed throat, sores, boils, wounds, cuts, bruises, and swellings. It actively inhibits FGF2, VEGFA, and ERK1, and promotes the inhibition of cancer development [127].
3.2.5. Aldehydes, Ketones, Quinones, and Anthraquinones
α-/β-Thujone
Thuja occidentalis is a member of the Cupressaceae family. α- and β-Thujone, compounds isolated from this plant, decrease cell viability, proliferation, and angiogenesis, as well as induce apoptosis in glioblastoma cells. They suppress the expression of angiogenic markers, such as VEGF, CD31, and Ang-4, and promote neoplasia regression [128].
Emodin
Aloe vera, a member of the Asphodelaceae family, is used as an alternative and folk medicine. Emodin, an active anthraquinone present in A. vera, inhibits cancer growth by suppressing the expression of MMP7, MMP9, VEGF, EMT, N-cadherin, β-catenin, and Snail. In addition, it inhibits the Wnt/β-catenin signaling pathway through downregulation of target genes, including c-Myc, Cyclin-D1, and TCF4 [129].
Plumbagin
Plumbago europaea, commonly known as leadwort, is a member of the Plumbaginaceae family. It is mainly found in Central Asia. Its root is vesicant, sialagogue, odontalgic, emetic, and acrid. Chewing its root is beneficial to cure toothache. Plumbagin, an active compound of this plant, exerts an anti-angiogenesis effect by downregulating the PI3K/Akt, VEGF/KDR, and angiopoietins/Tie2 pathways and factors related with cancer angiogenesis and tumor cells, including bFGF, ET-1, CTFG, and VEGFB [130].
3.2.6. Alkaloids
Berberine
Coptis chinensis belongs to the Ranunculaceae family and is used as a folk remedy to cure several diseases. Berberine, an active constituent of this plant, exerts its role in inhibiting cancer through an antiangiogenic mechanism; it inhibits VEGF expression in HUVECs with little toxicity [121].
Sinomenine
Sinomenium acutum is a member of the family Menispermaceae and used as a folk remedy to cure various diseases. Sinomenine, an active alkaloid isolated from this plant, has been identified as a potential anticancer and anti-invasion agent. It induces S-phase arrest and blocks clone formation to prevent proliferation. In osteosarcoma, it markedly inhibits metastasis and invasion with little toxicity. The mechanisms involved in its invasion inhibition include the suppression of STAT3 and CXCR4 phosphorylation, as well as downregulation of VEGF, RANKL, MMP2, and MMP9 expression [131].
Capsaicin
Capsaicin, an alkaloid/amide derivative, is a dietary-cancer-preventing agent found in Capsicum frutescens. It protects against tumor development and progression through different signaling pathways. It prevents melanoma cell proliferation by inhibiting the expression of VEGF. It downregulates the activation of focal adhesion kinase. It increases the degradation of hypoxia-inducible factor-1α and ultimately reduces VEGF expression [132]. Therefore, capsaicin is a potential anticancer agent interlinked with VEGF and VEGF-promoting factors.
3.2.7. Others
α-hydroxy Succinamic Acid
Eugenia jambolana fruit, commonly known as Jamun, is broadly found in the Asian sub-continent. It is also distributed in other areas of the world, such as Madagascar and South America. The fruit pulp contains malvidin-diglucoside, petunidin, delphinidin, α-hydroxy succinamic acid, and anthocyanin. Both its seed and fruit pulp have a long history of use as medicines. Several of their pharmacological activities have been studied, including antidiabetic, anticancer, antiviral, and antibacterial activities. In vitro studies indicated that an ethyl acetate extract of E. jambolana exerts cytotoxic activity and inhibits cell proliferation and tube formation. In vivo studies indicated that the plant lowers body weight, cell number, and VEGF secretion. All these findings indicate the potency of E. jambolana as an anti-angiogenesis and pro-apoptotic agent [133].
Lectin
Praecitrullus fistulosus is a tropical medicinal and vegetable plant belonging to the Cucurbitaceae family. Lectin, a glycoprotein isolated from the fruit sap of P. fistulosus, exhibits its potential role against cancer development by decreasing VEGF secretion and inhibiting the expression of MMP2 and MMP9. Interestingly, it does not exhibit any side effects in normal mice [134].
Odisolane
Morus alba fruit is commonly known as mulberry, which is an edible fruit possessing emetic, anthelmintic, expectorant, odontalgic, laxative, tonic, and sedative properties. Odisolane, a novel oxolane derivative identified from mulberry fruit, exerts an anti-angiogenesis effect for cancer treatment by suppressing the protein expression of VEGF, p-Akt, and p-ERK [135].
PRP-S16
Phellinus ribis belongs to the Hymenochaetaceae family. PRP-S16 is a sulfated polysaccharide, which, using the chlorosulfonic acid method, is derived by sulfation from a glucan obtained from Phellinus ribis. It inhibits the proliferation, migration, and tube formation of cancer, as well as reduces the expression of VEGF, VEGFR-1, VEGFR-2, Akt, and ERK1/2 to inhibit cancer growth [136].
Sulforaphane
Broccoli and cauliflower, members of the cruciferous family, are famous vegetables around the world. Recently, research has revealed that sulforaphane, a member of the isothiocyanate group, is produced from glucoraphanin hydrolysis through myrosinase and has a promising anticancer effect [137]. It inhibits cancer cell angiogenesis through inhibiting HIF-1α and VEGF expression as well as the migration of human colon cancer cells [138]. Recently, research has revealed that in hepatocellular carcinoma, it exerts its anti-angiogenesis effect though suppressing the STAT3/HIF-1α/VEGF signaling network [139]. Moreover, human clinical studies have proven that it has a chemopreventive effect and can be added as a dietary supplement to slow down cancer progression.
-Patrick
Boron Inhibits Tumor-induced Angiogenesis
Study: Cannabidiol Inhibits the Proliferation and Invasiveness of Prostate Cancer Cells 
