Propolis, a sticky material that honeybees collect from living plants, has been used for its pharmaceutical properties since ancient times. In this study, we examined the effects of ethanol extracts of Korean propolis (EEKP) from various geographic regions on the inhibition of angiogenesis, both in vitro and in vivo. The effects of EEKP were tested on in vitro models of angiogenesis, that is, tube formation and proliferation of human umbilical vein endothelial cells (HUVECs). All EEKP samples exhibited significant inhibitory effects on tube formation of HUVECs in a concentration-dependent manner (6.25-25 μg/mL). In addition, two EEKP samples, prepared from Uijeongbu and Pyoseon propolis, significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-25 μg/mL). Furthermore, in an in vivo angiogenesis assay using the chick embryo chorioallantoic membrane (CAM) system, we found that the two EEKP samples significantly reduced the number of newly formed vessels. These results indicate that Korean propolis may have potential applications in the prevention and treatment of angiogenesis-related diseases such as cancer.
FolkmanJ. (1971) Tumor angiogenesis: therapeutic implications. The New England Journal of Medicine, 285, 1182–1186.
2.
NaumovGN, AkslenLA, FolkmanJ. (2006) Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch. Cell Cycle, 5, 1779–1787.
3.
TosettiF, FerrariN, De FloraS, AlbiniA. (2002) Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents. FASEB Journal, 16, 2–14.
4.
BankovaV, PopovaM, TrushevaB. (2006) Plant sources of propolis: an update from a chemist's point of view. Natural Product Communications, 1, 1023–1028.
5.
BanskotaAH, TezukaY, KadotaS. (2001) Recent progress in pharmacological research of propolis. Phytotherapy Research, 15, 561–571.
6.
KujumgievA, TsvetkovaI, SerkedjievaY, BankovaV, ChristovR, PopovS. (1999) Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. Journal of Ethnopharmacology, 64, 235–240.
7.
VeraN, SolorzanoE, OrdoñezR, MaldonadoL, BedascarrasbureE, IslaMI. (2011) Chemical composition of Argentinean propolis collected in extreme regions and its relation with antimicrobial and antioxidant activities. Natural Product Communications, 6, 823–827.
8.
AmorosM, LurtonE, BoustieJ, GirreL, SauvagerF, CormierM. (1994) Comparison of the anti-herpes simplex virus activities of propolis and 3-methyl-but-2-enyl caffeate. Journal of Natural Products, 57, 644–647.
9.
MuradJM, CalviSA, SoaresAM, BankovaV, SforcinJM. (2002) Effect of propolis from Brazil and Bulgaria in fungicidal activity of mactophages against Paracoccidioides brasiliensis. Journal of Ethnopharmacology, 79, 331–334.
10.
WangL, MineshitaS, GaI, ShigematsuT, MatsunoT. (1993) Antiinflammatory effect of propolis. Japanese Journal of Clinical Pharmacology and Therapeutics, 24, 223–224.
11.
BanskotaAH, TezukaY, AdnyanaIK, IshiiE, MidorikawaK, MatsushigeK, KadotaS. (2001) Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis. Phytomedicine, 8, 16–23.
12.
OršolićN, TerzićS, MihaljevićŽ, ŠverL, BasićI. (2005) Effects of local administration of propolis and its polyphenolic compounds on tumor formation and growth. Biological and Pharmaceutical Bulletin, 28, 1928–1933.
13.
LiF, AwaleS, TezukaY, KadotaS. (2010) Cytotoxicity of constituents from Mexican propolis against a panel of six different cancer cell lines. Natural Product Communications, 5, 1601–1606.
14.
SchellerS, KrolW, SwiacikJ, OwczarekS, GabrysJ, ShaniJ. (1989) Antitumoral property of ethanolic extract of propolis in mice-bearing Ehrlich carcinoma, as compared to bleomycin. Zeitschriftfür Naturforschung, 44c, 1063–1065.
15.
RussoA, CardileV, SanchezF, TroncosoN, VanellaA, GarbarinoJA. (2004) Chilean propolis: antioxidant activity and antiproliferative action in human tumor cell lines. Life Sciences, 76, 545–558.
16.
Nieva MorenoMI, ZampiniIC, OrdóñezRM, JaimeGS, VattuoneMA, IslaMI. (2005) Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina. Journal of Agricultural and Food Chemistry, 53, 8957–8962.
17.
BurdockGA. (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food and Chemical Toxicology, 36, 347–363.
18.
AhnMR, KunimasaK, OhtaT, KumazawaS, KamihiraM, KajiK, UtoY, HoriH, NagasawaH, NakayamaT. (2007) Suppression of tumor-induced angiogenesis by Brazilian propolis: Major component artepillin C inhibits in vitro tube formation and endothelial cell proliferation. Cancer Letters, 252, 235–243.
19.
KunimasaK, AhnMR, KobayashiT, EguchiR, KumazawaS, FujimoriY, NakanoT, NakayamaT, KajiK, OhtaT. (2011) Brazilian propolis suppresses angiogenesis by inducing apoptosis in tube-forming endothelial cells through inactivation of survival signal ERK1/2. Evidence-Based Complementary and Alternative Medicine, doi:10.1093/ecam/nep024.
20.
KumazawaS, HamasakaT, NakayamaT. (2004) Antioxidant activity of propolis of various geographic origins. Food Chemistry, 84, 329–339.
21.
ChoiSJ, ShimomuraK, KumazawaS, AhnMR. (2013) Antioxidant properties and phenolic composition of propolis from diverse geographic regions in Korea. Food Science and Technology Research, 19, 211–222.
22.
AhnMR, KumazawaS, UsuiY, NakamuraJ, MatsukaM, ZhuF, NakayamaT. (2007) Antioxidant activity and constituents of propolis collected in various areas of China. Food Chemistry, 101, 1383–1392.
23.
HatanoA, NonakaT, YoshinoM, AhnMR, TazawaS, ArakiY, KumazawaS. (2012) Antioxidant activity and phenolic constituents of red propolis from Shandong, China. Food Science and Technology Research, 18, 577–584.
24.
KumazawaS, AhnMR, FujimotoT, KatoM. (2010) Radical-scavenging activity and phenolic constituents of propolis from different regions of Argentina. Natural Product Research, 24, 804–812.
25.
MarcucciMC. (1995) Propolis: Chemical composition, biological properties and therapeutic activity. Apidologie, 26, 83–99.
26.
KimYH, ChungHJ. (2011) The effects of Korean propolis against foodborne pathogens and transmission electron microscopic examination. New Biotechnology, 28, 713–718.
27.
EomHS, LeeEJ, YoonBS, YooBS. (2010) Propolis inhibits the proliferation of human leukaemia HL-60 cells by inducing apoptosis through the mitochondrial pathway. Natural Product Research, 24, 375–386.
28.
OikawaT, HirotaniK, NakamuraO, ShudoK, HiragunA, IwaguchiT. (1989) A highly potent antiangiogenic activity of retinoids. Cancer Letters, 48, 157–162.
29.
MarcucciMC, BankovaV. (1999) Chemical composition, plant origin and biological activity of Brazilian propolis. Current Topics in Phytochemistry, 2, 115–123.
30.
KahkonenMP, HopiaAI, VuorelaHJ, RauhaJP, PihlajaK, KujalaTS, HeinonenM. (1999) Antioxidant activity of plant extracts containing phenolic compounds. Journal of Agricultural and Food Chemistry, 47, 3954–3962.
31.
MetodiewaD, JaiswalAK, CenasN, DickancaitéE, Segura-AguilarJ. (1999) Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Radical Biology and Medicine, 26, 107–116.
32.
CorvazierE, MacloufJ. (1985) Interference of some flavonoids and non-steroidal anti-inflammatory drugs with oxidative metabolism of arachidonic acid by human platelets and neutrophils. Biochimica et Biophysica Acta, 835, 315–321.
33.
IguraK, OhtaT, KurodaY, KajiK. (2001) Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Letters, 171, 11–16.
34.
GrunbergerD, BanerjeeR, EisingerK, OltzEM, EfrosL, CaldwellM, EstevezV, NakanishiK. (1988) Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia, 44, 230–232.
35.
OzturkG, GinisZ, AkyolS, ErdenG, GurelA, AkyolO. (2012) The anticancer mechanism of caffeic acid phenethyl ester (CAPE): review of melanomas, lung and prostate cancers. European Review for Medical and Pharmacological Sciences, 16, 2064–2068.
36.
RaoCV, DesaiD, KaulB, AminS, ReddyBS. (1992) Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. Chemico-Biological Interactions, 84, 277–290.
37.
MichaluartP, MasferrerJL, CarothersAM, SubbaramaiahK, ZweifelBS, KoboldtC, MestreJR, GrunbergerD, SacksPG, TanabeT, DannenbergAJ. (1999) Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Research, 59, 2347–2352.
38.
AhnMR, KunimasaK, KumazawaS, NakayamaT, KajiK, UtoY, HoriH, NagasawaH, OhtaT. (2009) Correlation between antiangiogenic activity and antioxidant activity of various components from propolis. Molecular Nutrition and Food Research, 53, 643–651.
39.
FolkmanJ, ShingY. (1992) Angiogenesis. Journal of Biological Chemistry, 267, 10931–10934.
KunimasaK, KobayasiT, SugiyamaS, KajiK, OhtaT. (2008) Indole-3-carbinol suppresses tumor-induced angiogenesis by inhibiting tube formation and inducing apoptosis. Bioscience, Biotechnology, and Biochemistry, 72, 2243–2246.
42.
KimJH, LeeBJ, KimJH, YuYS, KimKW. (2009) Antiangiogenic effect of caffeic acid on retinal neovascularization. Vascular Pharmacology, 51, 262–267.
43.
WangS, YoonYC, SungMJ, HurHJ, ParkJH. (2012) Antiangiogenic properties of cafestol, a coffee diterpene, in human umbilical vein endothelial cells. Biochemical and Biophysical Research Communications, 421, 567–571.
44.
ShimamuraM, HazatoT, AshinoH, YamamotoY, IwasakiE, TobeH, YamamotoK, YamamotoS. (2001) Inhibition of angiogenesis by humulone, a bitter acid from beer hop. Biochemical and Biophysical Research Communications, 289, 220–224.
