Top

Published in:

01-03-2014 | Original Contribution

Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion

Authors: Simona Dinicola, Alessia Pasqualato, Alessandra Cucina, Pierpaolo Coluccia, Francesca Ferranti, Rita Canipari, Angela Catizone, Sara Proietti, Fabrizio D’Anselmi, Giulia Ricci, Alessandro Palombo, Mariano Bizzarri

Published in: European Journal of Nutrition | Issue 2/2014

Abstract

Background and aim

Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion.

Methods

After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, β-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. β-Catenin localization was observed by confocal microscopy.

Results

We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering β-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9.

Conclusions

These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.

Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRef

Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904CrossRef

Bogenrieder T, Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22:6524–6536CrossRef

Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:RA32–RA40

Alexander CM, Werb Z (1991) Extracellular matrix degradation. Plenum Press, New York, pp 255–302

Mignatti P, Rifkin DB (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73:161–195

Danø K, Andreasen PA, Grøndahl-Hansen J et al (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44:139–266CrossRef

Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67CrossRef

Lin KL, Tsai PC, Hsieh CY et al (2011) Antimetastatic effect and mechanism of ovatodiolide in MDA-MB-231 human breast cancer cells. Chem Biol Interact 194:148–158CrossRef

10.

Jiang P, Enomoto A, Takahashi M (2009) Cell biology of the movement of breast cancer cells: intracellular signalling and the actin cytoskeleton. Cancer Lett 284:122–130CrossRef

11.

Vignjevic D, Kojima S, Aratyn Y et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875CrossRef

12.

Edwards RA, Bryan J (1995) Fascins, a family of actin bundling proteins. Cell Motil Cytoskelet 32:1–9CrossRef

13.

Vignjevic D, Schoumacher M, Gavert N et al (2007) Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res 67:6844–6853CrossRef

14.

Brabletz T, Jung A, Hermann K et al (1998) Nuclear overexpression of the oncoprotein β-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract 194:701–704CrossRef

15.

Gavert N, Conacci-Sorrell M, Gast D et al (2005) L1, a novel target of h-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 168:633–642CrossRef

16.

Al-Alwan M, Olabi S, Ghebeh H et al (2011) Fascin is a key regulator of breast cancer invasion that acts via the modification of metastasis-associated molecules. PLoS One 6:e27339CrossRef

17.

Westermarck J, Kähäri VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792

18.

Lokeshwar BL (1999) MMP inhibition in prostate cancer. Ann NY Acad Sci 878:271–289CrossRef

19.

Brawley OW, Barnes S, Parnes H (2001) The future of prostate cancer prevention. Ann NY Acad Sci 952:145–152CrossRef

20.

Palmer S (1985) Diet, nutrition, and cancer. Prog Food Nutr Sci 9:283–341

21.

Dinicola S, Cucina A, Pasqualato A et al (2010) Apoptosis-inducing factor and caspase-dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2. Br J Nutr 104:824–832CrossRef

22.

Dinicola S, Cucina A, Pasqualato A et al (2012) Antiproliferative and apoptotic effects triggered by grape seed extract (GSE) versus epigallocatechin and procyanidins on colon cancer cell lines. Int J Mol Sci 13:651–664CrossRef

23.

Dinicola S, Mariggiò MA, Morabito C et al (2013) Grape seed extract triggers apoptosis in Caco-2 human colon cancer cells through reactive oxygen species and calcium increase: extracellular signal-regulated kinase involvement. Br J Nutr. doi:10.1017/S0007114512006095

24.

Sharma G, Tyagi AK, Singh RP et al (2004) Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells. Breast Cancer Res Treat 85:1–12CrossRef

25.

Cavaliere C, Foglia P, Gubbiotti R et al (2008) Rapid-resolution liquid chromatography/mass spectrometry for determination and quantitation of polyphenols in grape berries. Rapid Commun Mass Spectrom 22:3089–3099CrossRef

26.

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685CrossRef

27.

Belin D, Godeau F, Vassalli JD (1984) Tumor promoter PMA stimulates the synthesis and secretion of mouse pro-urokinase in MSV-transformed 3T3 cells: this is mediated by an increase in urokinase mRNA content. EMBO J 3:1901–1906

28.

Nandakumar V, Singh T, Katiyar SK (2008) Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett 269:378–387CrossRef

29.

Joshi SS, Kuszynski CA, Bagchi D (2001) The cellular and molecular basis of health benefits of grape seed proanthocyanidin extract. Curr Pharm Biotechnol 2:187–200CrossRef

30.

Saeki K, Hayakawa S, Isemura M et al (2000) Importance of a pyrogallol-type structure in catechin compounds for apoptosis-inducing activity. Phytochemistry 53:391–394CrossRef

31.

Wu PP, Kuo SC, Huang WW et al (2009) (-)-Epigallocatechin gallate induced apoptosis in human adrenal cancer NCI-H295 cells through caspase-dependent and caspase-independent pathway. Anticancer Res 29:1435–1442

32.

Ling H, Zhang Y, Ng KY et al (2011) Pachymic acid impairs breast cancer cell invasion by suppressing nuclear factor-κB-dependent matrix metalloproteinase-9 expression. Breast Cancer Res Treat 126:609–620CrossRef

33.

Ko HS, Lee HJ, Kim SH et al (2012) Piceatannol suppresses breast cancer cell invasion through the Inhibition of MMP-9: involvement of PI3K/AKT and NF-κB Pathways. J Agric Food Chem 60:4083–4089CrossRef

34.

Kim S, Han J, Lee SK et al (2011) Berberine suppresses the TPA-induced MMP-1 and MMP-9 expressions through the inhibition of PKC-α in breast cancer cells. J Surg Res 176:21–29CrossRef

35.

Vayalil PK, Mittal A, Katiyar SK (2004) Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with the inhibition of activation of MAPK and NF kappa B. Carcinogenesis 25:987–995CrossRef

36.

Vayalil PK, Katiyar SK (2004) Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells. Prostate 59:33–42CrossRef

37.

Duffy MJ, Maguire TM, Hill A et al (2000) Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2:252–257CrossRef

38.

Zucker S, Hymowitz M, Conner C et al (1999) Measurement of matrix metalloproteinases and tissue inhibitors of metalloproteinases in blood and tissues. Clinical and experimental applications. Ann NY Acad Sci 878:212–227CrossRef

39.

Yang SF, Chen MK, Hsieh YS et al (2010) Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases. Food Chem Toxicol 48:1052–1058CrossRef

40.

Aguirre Ghiso JA, Alonso DF, Farías EF et al (1999) Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur J Biochem 263:295–304CrossRef

41.

Sliva D (2004) Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Targets 4:327–336CrossRef

42.

Takada Y, Singh S, Aggarwal BB (2004) Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappaB-mediated gene expression and up-regulation of apoptosis. J Biol Chem 279:15096–15104CrossRef

43.

Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208CrossRef

44.

Snyder M, Huang XY, Zhang JJ (2011) Signal transducers and activators of transcription 3 (STAT3) directly regulates cytokine-induced fascin expression and is required for breast cancer cell migration. J Biol Chem 286:38886–38893CrossRef

45.

Adams JC (2004) Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 16:590–596CrossRef

46.

Machesky LM, Li A (2010) Fascin: invasive filopodia promoting metastasis. Commun Integr Biol 3:263–270CrossRef

47.

Jamieson C, Sharma M, Henderson BR (2012) Wnt signaling from membrane to nucleus: β-catenin caught in a loop. Int J Biochem Cell Biol 44:847–850CrossRef

48.

Valenta T, Hausmann G, Basler K (2012) The many faces and functions of β-catenin. EMBO J 31:2714–2736CrossRef

Title: Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion
Authors: Simona Dinicola
Alessia Pasqualato
Alessandra Cucina
Pierpaolo Coluccia
Francesca Ferranti
Rita Canipari
Angela Catizone
Sara Proietti
Fabrizio D’Anselmi
Giulia Ricci
Alessandro Palombo
Mariano Bizzarri
Publication date: 01-03-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 2/2014
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-013-0542-6

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion

Abstract

Background and aim

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background and aim

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2014

Acute effects of high-protein versus normal-protein isocaloric meals on satiety and ghrelin

Effect of green tea on postprandial antioxidant capacity, serum lipids, C-reactive protein and glucose levels in patients with coronary artery disease

Estimated dietary intakes and sources of flavanols in the German population (German National Nutrition Survey II)

In vitro investigation of the bioaccessibility of carotenoids from raw, frozen and boiled red chili peppers (Capsicum annuum)

Validity of food frequency questionnaire-based estimates of long-term long-chain n-3 polyunsaturated fatty acid intake

Dietary walnut oil modulates liver steatosis in the obese Zucker rat

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page