Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition

Title
Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition
Author(s)
김정애김미라[김미라]김옥[김옥]Nguyen Thi Thuy Phuong[Nguyen Thi Thuy Phuong]Nguyen Thi Thuy Phuong[Nguyen Thi Thuy Phuong]오원근[오원근]배기완[배기완]강건욱[강건욱]
Keywords
PROLYL ISOMERASE PIN1; CELL-CYCLE PROGRESSION; TRANSCRIPTIONAL ACTIVITY; RED WINE; C-JUN; RESVERATROL; INDUCTION; E2F; EXPRESSION; TARGET
Issue Date
201210
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.50, no.10, pp.3625 - 3634
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)alpha 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. (C) 2012 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27176http://dx.doi.org/10.1016/j.fct.2012.07.027
ISSN
0278-6915
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