Inhibition of angiogenesis by quercetin in tamoxifen-resistant breast cancer cells

Title
Inhibition of angiogenesis by quercetin in tamoxifen-resistant breast cancer cells
Author(s)
오수진[오수진]김옥[김옥]이종숙김정애김미라[김미라]김미라[김미라]최홍석[최홍석]심정현[심정현]강건욱[강건욱]김용철[김용철]
Keywords
ENDOTHELIAL GROWTH-FACTOR; PROLYL ISOMERASE PIN1; TRANSCRIPTIONAL ACTIVITY; DIETARY FLAVONOIDS; SOLID TUMORS; EXPRESSION; INDUCTION; OVEREXPRESSION; THERAPY; PATHWAY
Issue Date
201011
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.48, no.11, pp.3227 - 3234
Abstract
Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem among breast cancer patients. Previously, we have reported that TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) showed increased angiogenic intensity through Pin1-dependent vascular endothelial growth factor (VEGF) production. Among six flavonoids tested in the current study. VEGF gene transcription in MCF-7 cells with stable Pin1 overexpression was inhibited most effectively by quercetin. Reporter gene assays using minimal reporters containing hypoxia response elements and activator protein-1 (AP-1) elements revealed that the activities of hypoxia inducible factor-1 alpha (HIF-1 alpha) and AP-1, key transcription factors for VEGF gene transcription, were suppressed by quercetin. Western blot analyses confirmed that the increased nuclear levels of c-Jun and HIF-1 alpha in TAMR-MCF-7 cells were blocked by quercetin. Moreover, quercetin inhibited the enhanced VEGF secretion and Pin1 expression in TAMR-MCF-7 cells, which was dependent on its phosphatidyl inositol 3-kinase inhibiting effect. Chick chorioallantoic membrane assays demonstrated that the enhanced angiogenesis intensity of TAMR-MCF-7 cells was also suppressed significantly by quercetin. These results demonstrate that quercetin may have therapeutic potential for the treatment of TAM-resistant breast cancer via Pin1 inhibition. (C) 2010 Elsevier Ltd. All rights reserved,
URI
http://hdl.handle.net/YU.REPOSITORY/23377http://dx.doi.org/10.1016/j.fct.2010.08.028
ISSN
0278-6915
Appears in Collections:
약학대학 > 약학부 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE