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Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF\u20107 cells. MCF\u20107 cells were treated with different concentrations of TAM and\/or CAPE for 48\u2009h. This novel combination exerted synergistic cytotoxic effects against MCF\u20107 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl\u20102 and Beclin 1 expression levels. However, the mammalian microtubule\u2010associated protein light chain LC 3\u2010II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.<\/jats:p>","DOI":"10.1155\/2016\/3017108","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T21:37:01Z","timestamp":1448919421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF\u20107 Breast Cancer Cells"],"prefix":"10.1155","volume":"2016","author":[{"given":"Tarek K.","family":"Motawi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy A.","family":"Abdelazim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebatallah A.","family":"Darwish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Elbaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samia A.","family":"Shouman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,30]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20006"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp322"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci57152"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210749"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.1928"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.657"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf010830b"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.33.2028"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1995.0057"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2008.01.008"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.cad.0000224441.01082.bb"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.45.253"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000159843"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2011.04.012"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2006.07.007"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl066"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/82.13.1107"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47344-9"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cber.187901201117"},{"key":"e_1_2_7_24_2","first-page":"3583","article-title":"Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase","volume":"43","author":"Osborne C. 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