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Erschienen in: European Journal of Nutrition 2/2014

01.03.2014 | Original Contribution

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

verfasst von: 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

Erschienen in: European Journal of Nutrition | Ausgabe 2/2014

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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.
Literatur
1.
Zurück zum Zitat Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRef Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRef
2.
Zurück zum Zitat Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904CrossRef Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12:895–904CrossRef
3.
Zurück zum Zitat Bogenrieder T, Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22:6524–6536CrossRef Bogenrieder T, Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22:6524–6536CrossRef
4.
Zurück zum Zitat Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:RA32–RA40 Jezierska A, Motyl T (2009) Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit 15:RA32–RA40
5.
Zurück zum Zitat Alexander CM, Werb Z (1991) Extracellular matrix degradation. Plenum Press, New York, pp 255–302 Alexander CM, Werb Z (1991) Extracellular matrix degradation. Plenum Press, New York, pp 255–302
6.
Zurück zum Zitat Mignatti P, Rifkin DB (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73:161–195 Mignatti P, Rifkin DB (1993) Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73:161–195
7.
Zurück zum Zitat Danø K, Andreasen PA, Grøndahl-Hansen J et al (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44:139–266CrossRef Danø K, Andreasen PA, Grøndahl-Hansen J et al (1985) Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44:139–266CrossRef
8.
Zurück zum Zitat Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67CrossRef Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67CrossRef
9.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Vignjevic D, Kojima S, Aratyn Y et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875CrossRef Vignjevic D, Kojima S, Aratyn Y et al (2006) Role of fascin in filopodial protrusion. J Cell Biol 174:863–875CrossRef
12.
Zurück zum Zitat Edwards RA, Bryan J (1995) Fascins, a family of actin bundling proteins. Cell Motil Cytoskelet 32:1–9CrossRef Edwards RA, Bryan J (1995) Fascins, a family of actin bundling proteins. Cell Motil Cytoskelet 32:1–9CrossRef
13.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Westermarck J, Kähäri VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792 Westermarck J, Kähäri VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13:781–792
18.
Zurück zum Zitat Lokeshwar BL (1999) MMP inhibition in prostate cancer. Ann NY Acad Sci 878:271–289CrossRef Lokeshwar BL (1999) MMP inhibition in prostate cancer. Ann NY Acad Sci 878:271–289CrossRef
19.
Zurück zum Zitat Brawley OW, Barnes S, Parnes H (2001) The future of prostate cancer prevention. Ann NY Acad Sci 952:145–152CrossRef Brawley OW, Barnes S, Parnes H (2001) The future of prostate cancer prevention. Ann NY Acad Sci 952:145–152CrossRef
20.
Zurück zum Zitat Palmer S (1985) Diet, nutrition, and cancer. Prog Food Nutr Sci 9:283–341 Palmer S (1985) Diet, nutrition, and cancer. Prog Food Nutr Sci 9:283–341
21.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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/​S000711451200609​5
24.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685CrossRef Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685CrossRef
27.
Zurück zum Zitat 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 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.
Zurück zum Zitat Nandakumar V, Singh T, Katiyar SK (2008) Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett 269:378–387CrossRef Nandakumar V, Singh T, Katiyar SK (2008) Multi-targeted prevention and therapy of cancer by proanthocyanidins. Cancer Lett 269:378–387CrossRef
29.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Duffy MJ, Maguire TM, Hill A et al (2000) Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2:252–257CrossRef Duffy MJ, Maguire TM, Hill A et al (2000) Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2:252–257CrossRef
38.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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 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.
Zurück zum Zitat Sliva D (2004) Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Targets 4:327–336CrossRef Sliva D (2004) Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Targets 4:327–336CrossRef
42.
Zurück zum Zitat 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 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.
Zurück zum Zitat Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208CrossRef Aggarwal BB (2004) Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208CrossRef
44.
Zurück zum Zitat 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 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.
Zurück zum Zitat Adams JC (2004) Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 16:590–596CrossRef Adams JC (2004) Roles of fascin in cell adhesion and motility. Curr Opin Cell Biol 16:590–596CrossRef
46.
Zurück zum Zitat Machesky LM, Li A (2010) Fascin: invasive filopodia promoting metastasis. Commun Integr Biol 3:263–270CrossRef Machesky LM, Li A (2010) Fascin: invasive filopodia promoting metastasis. Commun Integr Biol 3:263–270CrossRef
47.
Zurück zum Zitat 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 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.
Zurück zum Zitat Valenta T, Hausmann G, Basler K (2012) The many faces and functions of β-catenin. EMBO J 31:2714–2736CrossRef Valenta T, Hausmann G, Basler K (2012) The many faces and functions of β-catenin. EMBO J 31:2714–2736CrossRef
Metadaten
Titel
Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion
verfasst von
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
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 2/2014
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-013-0542-6

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