Grape Polyphenols Inhibit Akt/Mammalian Target of Rapamycin Signaling and Potentiate the Effects of Gefitinib in Breast Cancer

REFERENCES

• Siegel , R , Ward , E , Brawley , O and Jemal , A . 2011 . Cancer statistics, 2011: The impact of eliminating socioeconomic and racial disparities on premature cancer deaths . CA Cancer J Clin , 61 : 212 – 236 .
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo , A M , Morales-Vasquez , F and Hortobagyi , G N . 2007 . Overview of resistance to systemic therapy in patients with breast cancer . Adv Exp Med Biol , 608 : 1 – 22 .
   PubMed Web of Science ®Google Scholar
• Engelman , J A and Settleman , J . 2008 . Acquired resistance to tyrosine kinase inhibitors during cancer therapy . Curr Opin Genet Dev , 18 : 73 – 79 .
   PubMed Web of Science ®Google Scholar
• Ricciardi , S , Tomao , S and de , M F . 2009 . Toxicity of targeted therapy in non-small-cell lung cancer management . Clin Lung Cancer , 10 : 28 – 35 .
   PubMed Web of Science ®Google Scholar
• Kaur , M , Agarwal , C and Agarwal , R . 2009 . Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products . J Nutr , 139 : 1806S – 1812S .
   PubMed Web of Science ®Google Scholar
• Hakimuddin , F , Paliyath , G and Meckling , K . 2004 . Selective cytotoxicity of a red grape wine flavonoid fraction against MCF-7 cells . Breast Cancer Res Treat , 85 : 65 – 79 .
   PubMed Web of Science ®Google Scholar
• Harris , D M , Besselink , E , Henning , S M , Go , V L and Heber , D . 2005 . Phytoestrogens induce differential estrogen receptor alpha- or beta-mediated responses in transfected breast cancer cells . Exp Biol Med (Maywood) , 230 : 558 – 568 .
   PubMed Web of Science ®Google Scholar
• Singletary , K W , Stansbury , M J , Giusti , M , van Breemen , R B Wallig , M . 2003 . Inhibition of rat mammary tumorigenesis by concord grape juice constituents . J Agric Food Chem , 51 : 7280 – 7286 .
   PubMed Web of Science ®Google Scholar
• Singh , R P , Tyagi , A K , Dhanalakshmi , S , Agarwal , R and Agarwal , C . 2004 . Grape seed extract inhibits advanced human prostate tumor growth and angiogenesis and upregulates insulin-like growth factor binding protein-3 . Int J Cancer , 108 : 733 – 740 .
   PubMed Web of Science ®Google Scholar
• Velmurugan , B , Singh , R P , Agarwal , R and Agarwal , C . 2010 . Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 rats . Mol Carcinog , 49 : 641 – 652 .
   PubMed Web of Science ®Google Scholar
• Kaur , M , Tyagi , A , Singh , R P , Sclafani , R A Agarwal , R . 2011 . Grape seed extract upregulates p21 (Cip1) through redox-mediated activation of ERK1/2 and posttranscriptional regulation leading to cell cycle arrest in colon carcinoma HT29 cells . Mol Carcinog , 50 : 553 – 562 .
   PubMed Web of Science ®Google Scholar
• Lu , J , Zhang , K , Chen , S and Wen , W . 2009 . Grape seed extract inhibits VEGF expression via reducing HIF-1alpha protein expression . Carcinogenesis , 30 : 636 – 644 .
   PubMed Web of Science ®Google Scholar
• Gescher , A J and Steward , W P . 2003 . Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum . Cancer Epidemiol Biomarkers Prev , 12 : 953 – 957 .
   PubMed Web of Science ®Google Scholar
• Meng , X , Maliakal , P , Lu , H , Lee , M J and Yang , C S . 2004 . Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after ingestion of pure compounds and grape juice . J Agric Food Chem , 52 : 935 – 942 .
   PubMed Web of Science ®Google Scholar
• Manach , C , Williamson , G , Morand , C , Scalbert , A and Remesy , C . 2005 . Bioavailability and bioefficacy of polyphenols in humans: I. Review of 97 bioavailability studies . Am J Clin Nutr , 81 : 230S – 242S .
   PubMed Web of Science ®Google Scholar
• Asensi , M , Medina , I , Ortega , A , Carretero , J Baño , M C . 2002 . Inhibition of cancer growth by resveratrol is related to its low bioavailability . Free Radic Biol Med , 33 : 387 – 398 .
   PubMed Web of Science ®Google Scholar
• Ferrer , P , Asensi , M , Segarra , R , Ortega , A Benlloch , M . 2005 . Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma . Neoplasia , 7 : 37 – 47 .
   PubMed Web of Science ®Google Scholar
• Soleas , G J , Grass , L , Josephy , P D , Goldberg , D M and Diamandis , E P . 2002 . A comparison of the anticarcinogenic properties of four red wine polyphenols . Clin Biochem , 35 : 119 – 124 .
   PubMed Web of Science ®Google Scholar
• Terao , J , Murota , K and Kawai , Y . 2011 . Conjugated quercetin glucuronides as bioactive metabolites and precursors of aglycone in vivo . Food Funct , 2 : 11 – 17 .
   PubMed Web of Science ®Google Scholar
• Andres-Lacueva , C , Macarulla , M T , Rotches-Ribalta , M , Boto-Ordóñez , M Urpi-Sarda , M . 2012 . Distribution of resveratrol metabolites in liver, adipose tissue, and skeletal muscle in rats fed different doses of this polyphenol . J Agric Food Chem , 60 : 4833 – 4840 .
   PubMed Web of Science ®Google Scholar
• Lotito , S B , Zhang , W J , Yang , C S , Crozier , A and Frei , B . 2011 . Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties . Free Radic Biol Med , 51 : 454 – 463 .
   PubMed Web of Science ®Google Scholar
• Perez-Vizcaino , F , Duarte , J and Santos-Buelga , C . 2012 . The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids . J Sci Food Agric , 92 : 1822 – 1825 .
   PubMed Web of Science ®Google Scholar
• Cimino , S , Sortino , G , Favilla , V , Castelli , T Madonia , M . 2012 . Polyphenols: key issues involved in chemoprevention of prostate cancer . Oxid Med Cell Longev , 2012
   PubMed Web of Science ®Google Scholar
• Levi , F , Pasche , C , Lucchini , F , Ghidoni , R Ferraroni , M . 2005 . Resveratrol and breast cancer risk . Eur J Cancer Prev , 14 : 139 – 142 .
   PubMed Web of Science ®Google Scholar
• Chan , S K , Hill , M E and Gullick , W J . 2006 . The role of the epidermal growth factor receptor in breast cancer . J Mammary Gland Biol Neoplasia , 11 : 3 – 11 .
   PubMed Web of Science ®Google Scholar
• Von , P J . 2004 . Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid tumors . Bull Cancer , 91 : E70 – E76 .
   PubMedGoogle Scholar
• Kosaka , T , Yamaki , E , Mogi , A and Kuwano , H . 2011 . Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer . J Biomed Biotechnol , 2011 : 165 – 214 .
   Google Scholar
• Yoshikawa , S , Kukimoto-Niino , M , Parker , L , Handa , N Terada , T . 2012 . Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor . Oncogene ,
   PubMed Web of Science ®Google Scholar
• Baselga , J , Albanell , J , Ruiz , A , Lluch , A Gascón , P . 2005 . Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer . J Clin Oncol , 23 : 5323 – 5333 .
   PubMed Web of Science ®Google Scholar
• Bernsdorf , M , Balslev , E , Lykkesfeldt , A E , Kroman , N Harder , E . 2011 . Value of post-operative reassessment of estrogen receptor alpha expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer . Breast Cancer Res Treat , 128 : 165 – 170 .
   PubMed Web of Science ®Google Scholar
• Osborne , C K , Neven , P , Dirix , L Y , Mackey , J R Robert , J . 2011 . Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study . Clin Cancer Res , 17 : 1147 – 1159 .
   PubMed Web of Science ®Google Scholar
• Bernsdorf , M , Ingvar , C , Jorgensen , L , Tuxen , M K Jakobsen , E H . 2011 . Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial . Breast Cancer Res Treat , 126 : 463 – 470 .
   PubMed Web of Science ®Google Scholar
• Knight , L A , Di , N F , Whitehouse , P , Mercer , S Sharma , M . 2004 . The in vitro effect of gefitinib (‘Iressa’) alone and in combination with cytotoxic chemotherapy on human solid tumours . BMC Cancer , 4 : 83
   PubMed Web of Science ®Google Scholar
• Dragowska , W H , Weppler , S A , Qadir , M A , Wong , L Y Franssen , Y . 2011 . The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing breast cancer cells and tumors irrespective of trastuzumab sensitivity . BMC Cancer , 11 : 420
   PubMed Web of Science ®Google Scholar
• Somlo , G , Martel , C L , Lau , S K , Frankel , P Ruel , C . 2012 . A phase I/II prospective, single arm trial of gefitinib, trastuzumab, and docetaxel in patients with stage IV HER-2 positive metastatic breast cancer . Breast Cancer Res Treat , 131 : 899 – 906 .
   PubMed Web of Science ®Google Scholar
• Massarweh , S , Tham , Y L , Huang , J , Sexton , K Weiss , H . 2011 . A phase II neoadjuvant trial of anastrozole, fulvestrant, and gefitinib in patients with newly diagnosed estrogen receptor positive breast cancer . Breast Cancer Res Treat , 129 : 819 – 827 .
   PubMed Web of Science ®Google Scholar
• Cristofanilli , M , Valero , V , Mangalik , A , Royce , M Rabinowitz , I . 2010 . Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer . Clin Cancer Res , 16 : 1904 – 1914 .
   PubMed Web of Science ®Google Scholar
• Gutteridge , E , Agrawal , A , Nicholson , R , Leung , C K Robertson , J . 2010 . The effects of gefitinib in tamoxifen-resistant and hormone-insensitive breast cancer: a phase II study . Int J Cancer , 126 : 1806 – 1816 .
   PubMed Web of Science ®Google Scholar
• Fridrich , D , Teller , N , Esselen , M , Pahlke , G and Marko , D . 2008 . Comparison of delphinidin, quercetin and (-)-epigallocatechin-3-gallate as inhibitors of the EGFR and the ErbB2 receptor phosphorylation . Mol Nutr Food Res , 52 : 815 – 822 .
   PubMed Web of Science ®Google Scholar
• Azios , N G and Dharmawardhane , S F . 2005 . Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer cells . Neoplasia , 7 : 128 – 140 .
   PubMed Web of Science ®Google Scholar
• Jeong , J H , An , J Y , Kwon , Y T , Li , L Y and Lee , Y J . 2008 . Quercetin-induced ubiquitination and down-regulation of Her-2/neu . J Cell Biochem , 105 : 585 – 595 .
   PubMed Web of Science ®Google Scholar
• O’Regan , R and Hawk , N N . 2011 . mTOR inhibition in breast cancer: unraveling the complex mechanisms of mTOR signal transduction and its clinical implications in therapy . Expert Opin Ther Targets , 15 : 859 – 872 .
   PubMed Web of Science ®Google Scholar
• Kopelovich , L , Fay , J R , Sigman , C C and Crowell , J A . 2007 . The mammalian target of rapamycin pathway as a potential target for cancer chemoprevention . Cancer Epidemiol Biomarkers Prev , 16 : 1330 – 1340 .
   PubMed Web of Science ®Google Scholar
• Dobashi , Y , Watanabe , Y , Miwa , C , Suzuki , S and Koyama , S . 2011 . Mammalian target of rapamycin: a central node of complex signaling cascades . Int J Clin Exp Pathol , 4 : 476 – 495 .
   PubMed Web of Science ®Google Scholar
• Shaw , R J . 2009 . LKB1 and AMP-activated protein kinase control of mTOR signalling and growth . Acta Physiol (Oxf) , 196 : 65 – 80 .
   PubMed Web of Science ®Google Scholar
• van der Heijden , M S and Bernards , R . 2010 . Inhibition of the PI3K pathway: hope we can believe in? . Clin Cancer Res , 16 : 3094 – 3099 .
   PubMed Web of Science ®Google Scholar
• Garg , A K , Buchholz , T A and Aggarwal , B B . 2005 . Chemosensitization and radiosensitization of tumors by plant polyphenols . Antioxid Redox Signal , 7 : 1630 – 1647 .
   PubMed Web of Science ®Google Scholar
• Olson , E R , Melton , T , Dickinson , S E , Dong , Z Alberts , D S . 2010 . Quercetin potentiates UVB-Induced c-Fos expression: implications for its use as a chemopreventive agent . Cancer Prev Res (Phila) , 3 : 876 – 884 .
   PubMed Web of Science ®Google Scholar
• Iqbal , M A and Bamezai , R N . 2012 . Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2 via inhibition of mammalian target of rapamycin . PLoS One , 7 : e36764
   PubMed Web of Science ®Google Scholar
• Van Aller , G S , Carson , J D , Tang , W , Peng , H Zhao , L . 2011 . Epigallocatechin gallate (EGCG), a major component of green tea, is a dual phosphoinositide-3-kinase/mTOR inhibitor . Biochem Biophys Res Commun , 406 : 194 – 199 .
   PubMed Web of Science ®Google Scholar
• He , X , Wang , Y , Zhu , J , Orloff , M and Eng , C . 2011 . Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling . Cancer Lett , 301 : 168 – 176 .
   PubMed Web of Science ®Google Scholar
• Schlachterman , A , Valle , F , Wall , K M , Azios , N G Castillo , L . 2008 . Combined resveratrol, quercetin, and catechin treatment reduces breast tumor growth in a nude mouse model . Transl Oncol , 1 : 19 – 27 .
   PubMed Web of Science ®Google Scholar
• Castillo-Pichardo , L , Martinez-Montemayor , M M , Martinez , J E , Wall , K M Cubano , L A . 2009 . Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols . Clin Exp Metastasis , 26 : 505 – 516 .
   PubMed Web of Science ®Google Scholar
• Phadke , P A , Vaidya , K S , Nash , K T , Hurst , D R and Welch , D R . 2008 . BRMS1 suppresses breast cancer experimental metastasis to multiple organs by inhibiting several steps of the metastatic process . Am J Pathol , 172 : 809 – 817 .
   PubMed Web of Science ®Google Scholar
• Yang , M , Baranov , E , Jiang , P , Sun , F X Li , X M . 2000 . Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases . Proc Natl Acad Sci USA , 97 : 1206 – 1211 .
   PubMed Web of Science ®Google Scholar
• Hayashi , Y , Matsushima , M , Nakamura , T , Shibasaki , M Hashimoto , N . 2012 . Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells . Biochem Biophys Res Commun , 417 : 169 – 174 .
   PubMed Web of Science ®Google Scholar
• Ferrer-Soler , L , Vazquez-Martin , A , Brunet , J , Menendez , J A De , L R . 2007 . An update of the mechanisms of resistance to EGFR-tyrosine kinase inhibitors in breast cancer: gefitinib (Iressa)-induced changes in the expression and nucleo-cytoplasmic trafficking of HER-ligands (Review) . Int J Mol Med , 20 : 3 – 10 .
   PubMed Web of Science ®Google Scholar
• Arpino , G , Gutierrez , C , Weiss , H , Rimawi , M Massarweh , S . 2007 . Treatment of human epidermal growth factor receptor 2-overexpressing breast cancer xenografts with multiagent HER-targeted therapy . J Natl Cancer Inst , 99 : 694 – 705 .
   PubMed Web of Science ®Google Scholar
• Wakeling , A E , Guy , S P , Woodburn , J R , Ashton , S E Curry , B J . 2002 . ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy . Cancer Res , 62 : 5749 – 5754 .
   PubMed Web of Science ®Google Scholar
• Murota , K and Terao , J . 2003 . Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism . Arch Biochem Biophys , 417 : 12 – 17 .
   PubMed Web of Science ®Google Scholar
• Bottner , M , Christoffel , J , Jarry , H and Wuttke , W . 2006 . Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats . J Endocrinol , 189 : 77 – 88 .
   PubMed Web of Science ®Google Scholar
• Saeed , S A , Connor , J D , Imran , Quadri , J Tasneem , S . 2007 . Inhibitors of phosphatidylinositide 3-kinase: effects on reactive oxygen species and platelet aggregation . Pharmacol Rep , 59 : 238 – 243 .
   PubMed Web of Science ®Google Scholar
• Gulati , N , Laudet , B , Zohrabian , V M , Murali , R and Jhanwar-Uniyal , M . 2006 . The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway . Anticancer Res , 26 : 1177 – 1181 .
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo , A M and Meric-Bernstam , F . 2010 . Metformin: a therapeutic opportunity in breast cancer . Clin Cancer Res , 16 : 1695 – 1700 .
   PubMed Web of Science ®Google Scholar
• Berstein , L M , Yue , W , Wang , J P and Santen , R J . 2011 . Isolated and combined action of tamoxifen and metformin in wild-type, tamoxifen-resistant, and estrogen-deprived MCF-7 cells . Breast Cancer Res Treat , 28 : 109 – 117 .
   Web of Science ®Google Scholar
• Hwang , J T , Kwon , D Y and Yoon , S H . 2009 . AMP-activated protein kinase: a potential target for the diseases prevention by natural occurring polyphenols . N Biotechnol , 26 : 17 – 22 .
   PubMed Web of Science ®Google Scholar
• Puissant , A , Robert , G , Fenouille , N , Luciano , F Cassuto , J P . 2010 . Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation . Cancer Res , 70 : 1042 – 1052 .
   PubMed Web of Science ®Google Scholar
• Lee , Y K , Park , S Y , Kim , Y M , Lee , W S and Park , O J . 2009 . AMP kinase/cycl– ooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin . Exp Mol Med , 41 : 201 – 207 .
   PubMed Web of Science ®Google Scholar
• Wong , A K , Howie , J , Petrie , J R and Lang , C C . 2009 . AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease . Clin Sci (Lond) , 116 : 607 – 620 .
   PubMed Web of Science ®Google Scholar
• Lehman , J A and Gomez-Cambronero , J . 2002 . Molecular crosstalk between p70S6k and MAPK cell signaling pathways . Biochem Biophys Res Commun , 293 : 463 – 469 .
   PubMed Web of Science ®Google Scholar
• Kapetanovic , I M , Muzzio , M , Huang , Z , Thompson , T N and McCormick , D L . 2011 . Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats . Cancer Chemother Pharmacol , 68 : 593 – 601 .
   PubMed Web of Science ®Google Scholar
• Yoo , Y J , Prenzler , P D , Saliba , A J and Ryan , D . 2011 . Assessment of some Australian red wines for price, phenolic content, antioxidant activity, and vintage in relation to functional food prospects . J Food Sci , 76 : C1355 – C1364 .
   PubMed Web of Science ®Google Scholar
• Faustino , R S , Sobrattee , S , Edel , A L and Pierce , G N . 2003 . Comparative analysis of the phenolic content of selected Chilean, Canadian and American Merlot red wines . Mol Cell Biochem , 249 : 11 – 19 .
   PubMed Web of Science ®Google Scholar