Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1

Huang,Shuangsheng; Yang,Ninggang; Liu,Yuanyuan; Gao,Jing; Huang,Tao; Hu,Lamei; Zhao,Jin; Li,Yongquan; Li,Caili; Zhang,Xiaosu

doi:10.3892/ijmm.2012.1147

Grape seed proanthocyanidins inhibit colon cancer-induced angiogenesis through suppressing the expression of VEGF and Ang1

Authors:
- Shuangsheng Huang
- Ninggang Yang
- Yuanyuan Liu
- Jing Gao
- Tao Huang
- Lamei Hu
- Jin Zhao
- Yongquan Li
- Caili Li
- Xiaosu Zhang
View Affiliations

Affiliations: Medical College of Northwest University for Nationalities, Lanzhou, Gansu, P.R. China, Department of Urology, Lanzhou First People's Hospital, Lanzhou, Gansu, P.R. China, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu, P.R. China, Institute of Pharmacology, School of Basic Medical Science, Lanzhou University, Lanzhou, Gansu, P.R. China
Published online on: October 1, 2012 https://doi.org/10.3892/ijmm.2012.1147
Pages: 1410-1416

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Tumor cells trigger angiogenesis through overexpression of various angiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang1). Therefore, inhibition of the expression of both VEGF and Ang1, the initial step of tumor angiogenesis, is a promising strategy for cancer chemoprevention and therapy. Grape seed proanthocyanidins (GSPs) are widely consumed dietary supplements that have antitumor activity. Due to their polymeric structure, GSPs are poorly absorbed along the gastrointestinal tract and can reach the colon at high concentrations, allowing these chemicals to act as chemopreventive agents for colon cancer. In the present study, we found that GSPs inhibited colon tumor-induced angiogenesis and, thus, the growth of colon tumor xenografts on the chick chorioallantoic membranes. The mechanisms of their action were related to inhibiting the expression of both VEGF and Ang1 through scavenging reactive oxygen species. Previous studies have demonstrated that the chemopreventive effects of GSPs on colon cancer are associated with their growth inhibitory and apoptosis-inducing effects. Our results demonstrate another mechanism by which GSPs inhibit colon tumor growth, which will be helpful for developing GSPs as a pharmacologically safe angiopreventive agent against colorectal cancer.

View Figures

View References

1.	J FolkmanRole of angiogenesis in tumor growth and metastasisSemin Oncol291518200210.1053/sonc.2002.3726312516034
2.	D HanahanJ FolkmanPatterns and emerging mechanisms of the angiogenic switch during tumorigenesisCell86353364199610.1016/S0092-8674(00)80108-78756718
3.	G BergersLE BenjaminTumorigenesis and the angiogenic switchNat Rev Cancer3401410200310.1038/nrc1093
4.	TP SzatrowskiCF NathanProduction of large amounts of hydrogen peroxide by human tumor cellsCancer Res5179479819911846317
5.	JL ArbiserJ PetrosR KlafterReactive oxygen generated by Nox1 triggers the angiogenic switchProc Natl Acad Sci USA99715720200210.1073/pnas.02263019911805326
6.	R SiegelD NaishadhamA JemalCancer statistics, 2012CA Cancer J Clin621029201210.3322/caac.20138
7.	W ChenH ZengR ZhengS ZhangJ HeCancer incidence and mortality in China, 2007Chin J Cancer Res2418201210.1007/s11670-012-0001-6
8.	G BlockB PattersonA SubarFruit, vegetables, and cancer prevention: a review of the epidemiological evidenceNutr Cancer18129199210.1080/016355892095142011408943
9.	Y SurhMolecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substancesMutat Res248305327199910.1016/S1383-5742(99)00057-510518003
10.	V NandakumarT SinghSK KatiyarMulti-targeted prevention and therapy of cancer by proanthocyanidinsCancer Lett269378387200810.1016/j.canlet.2008.03.04918457915
11.	M KaurC AgarwalR AgarwalAnticancer and cancer chemopreventive potential of grape seed extract and other grape-based productsJ Nutr1391806S1812S200910.3945/jn.109.10686419640973
12.	JP SpencerF ChaudryAS PannalaSK SraiE DebnamC Rice-EvansDecomposition of cocoa procyanidins in the gastric milieuBiochem Biophys Res Commun272236241200010.1006/bbrc.2000.274910872833
13.	LY RiosRN BennettSA LazarusC RémésyA ScalbertG WilliamsonCocoa procyanidins are stable during gastric transit in humansAm J Clin Nutr7611061110200212399286
14.	CG FragaPI OteizaDietary flavonoids: Role of (−)-epicatechin and related procyanidins in cell signalingFree Radic Biol Med518138232011
15.	RL PriorL GuOccurrence and biological significance of proanthocyanidins in the American dietPhytochemistry6622642280200510.1016/j.phytochem.2005.03.02515904940
16.	M RossiE NegriM ParpinelProanthocyanidins and the risk of colorectal cancer in ItalyCancer Causes Control21243250201010.1007/s10552-009-9455-320012183
17.	KW SingletaryB MelineEffect of grape seed proanthocyanidins on colon aberrant crypts and breast tumors in a rat dual-organ tumor modelNutr Cancer39252258200110.1207/S15327914nc392_1511759289
18.	H NomotoM IigoH HamadaS KojimaH TsudaChemoprevention of colorectal cancer by grape seed proanthocyanidin is accompanied by a decrease in proliferation and increase in apoptosisNutr Cancer498188200410.1207/s15327914nc4901_1115456639
19.	M KaurRP SinghM GuR AgarwalC AgarwalGrape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cellsClin Cancer Res1261946202200610.1158/1078-0432.CCR-06-146517062697
20.	AM EngelbrechtM MattheyseB EllisProanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell lineCancer Lett258144153200710.1016/j.canlet.2007.08.02017923279
21.	M KaurR MandairR AgarwalC AgarwalGrape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cellsNutr Cancer60Suppl 1S2S11200810.1080/0163558080238129519003575
22.	CP HsuYH LinCC ChouMechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cellsAnticancer Res29283289200919331163
23.	B VelmuruganRP SinghN KaulR AgarwalC AgarwalDietary feeding of grape seed extract prevents intestinal tumorigenesis in APC min/+ miceNeoplasia1295102201020072658
24.	S DinicolaA CucinaA PasqualatoApoptosis-inducing factor and caspase- dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2Br J Nutr104824832201010.1017/S000711451000152220540818
25.	M KaurA TyagiRP SinghRA SclafaniR AgarwalC AgarwalGrape seed extract upregulates p21 (Cip1) through redox-mediated activation of ERK1/2 and posttranscriptional regulation leading to cell cycle arrest in colon carcinoma HT29 cellsMol Carcinog50553562201110.1002/mc.20739
26.	B VelmuruganRP SinghR AgarwalC AgarwalDietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 ratsMol Carcinog49641652201020564341
27.	V VichaiK KirtikaraSulforhodamine B colorimetric assay for cytotoxicity screeningNat Protoc111121116200610.1038/nprot.2006.17917406391
28.	M HagedornS JaverzatD GilgesA MeyreB de LafargeA EichmannA BikfalviAccessing key steps of human tumor progression in vivo by using an avian embryo modelProc Natl Acad Sci USA10216431648200510.1073/pnas.040862210215665100
29.	M BalkeA NeumannC KerstingMorphologic characterization of osteosarcoma growth on the chick chorioallantoic membraneBMC Res Notes358201010.1186/1756-0500-3-5820202196
30.	PW HewettIdentification of tumour-induced changes in endothelial cell surface protein expression: an in vitro modelInt J Biochem Cell Biol33325335200110.1016/S1357-2725(01)00020-611312103
31.	H WangJA JosephQuantifying cellular oxidative stress by dichlorofluorescein assay using microplate readerFree Radical Biol Med27612616199910490282
32.	P SaharinenL EklundK PulkkiP BonoK AlitaloVEGF and angiopoietin signaling in tumor angiogenesis and metastasisTrends Mol Med17347362201110.1016/j.molmed.2011.01.01521481637
33.	RP SinghAK TyagimS DhanalakshmimR AgarwalmC AgarwalmGrape seed extract inhibits advanced human prostate tumor growth and angiogenesis and up-regulates insulin-like growth factor binding protein-3Int J Cancer108733740200410.1002/ijc.1162014696100
34.	MM HickeyMC SimonRegulation of angiogenesis by hypoxia and hypoxia-inducible factorsCurr Top Dev Biol76217257200610.1016/S0070-2153(06)76007-017118268
35.	WG Kaelin JrPJ RatcliffeOxygen sensing by metazoans: the central role of the HIF hydroxylase pathwayMol Cell30393402200810.1016/j.molcel.2008.04.00918498744
36.	EL BellTA KlimovaJ EisenbartThe Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species productionJ Cell Biol17710291036200710.1083/jcb.20060907417562787
37.	C XiaQ MengLZ LiuY RojanasakulXR WangBH JiangReactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factorCancer Res671082310830200710.1158/0008-5472.CAN-07-078318006827
38.	SS HuangNG YangYY LiuGrape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signalingNutrition Res32530536201210.1016/j.nutres.2012.05.01222901561