title: Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition.
abstract: Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem among estrogen-receptor-positive breast cancer patients. We have previously reported that TAM-resistant MCF-7 (TAMR-MCF-7) cells have elevated angiogenic potential via Pin1-dependent vascular endothelial growth factor (VEGF) production. Vitis amurensis grape consumed as wine and fruit contains several resveratrol-like stilbenes or oligostilbenes. In this study, we screened for the most active compound to inhibit VEGF production from V. amurensis. Among the tested compounds, amurensin G most potently suppressed VEGF production in TAMR-MCF-7 cells. The enhanced VEGF gene transcription in TAMR-MCF-7 cells was suppressed by amurensin G. Molecular analyses using reporter genes with hypoxia response elements and activator protein-1 (AP-1) elements, and western blots revealed that the activities and the nuclear levels of hypoxia inducible factor-1 (HIF-1)α and AP-1 in TAMR-MCF-7 cells were decreased by amurensin G. Moreover, amurensin G concentration-dependently inhibited protein expression and gene transcription of Pin1 in TAMR-MCF-7 cells, which was dependent on E2F1 inhibition. Chick chorioallantoic membrane assays confirmed that amurensin G had significant antiangiogenic and antitumor growth effects in TMAR-MCF-7 cells. These results demonstrate for the first time that amurensin G may have therapeutic potential for TAM-resistant breast cancer through blocking of Pin1-mediated VEGF gene transcription.
authors: College of Pharmacy, Yeungnam University, Daegu 712-749, Republic of Korea.
authors: Jung-Ae
authors: JA
authors: Kim
authors: Mi Ra
authors: MR
authors: Kim
authors: Ok
authors: O
authors: Kim
authors: Nguyen Thi Thuy
authors: NT
authors: Phuong
authors: Jieun
authors: J
authors: Yun
authors: Jieun
authors: J
authors: Yoon
authors: Won Keun
authors: WK
authors: Oh
authors: KiHwan
authors: K
authors: Bae
authors: Keon Wook
authors: KW
authors: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003986:Dibenzocycloheptenes / Q000737:chemistry / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009389:Neovascularization, Pathologic; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000737:chemistry / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003986:Dibenzocycloheptenes; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D051793:Hypoxia-Inducible Factor 1; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012118:Resorcinols; D042461:Vascular Endothelial Growth Factor A; C553921:amurensin G; D013629:Tamoxifen; D048031:JNK Mitogen-Activated Protein Kinases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase