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Title | Amurensin G inhibits angiogenesis and tumor growth of tamoxifen-resistant breast cancer via Pin1 inhibition |
Authors | J A Kim; M R Kim; O Kim; N T T Phuong; Ji Eun Yun; W K Oh; K Bae; K W Kang |
Publisher | Elsevier |
Issue Date | 2012 |
Citation | Food and Chemical Toxicology, vol. 50, no. 10, pp. 3625-3634 |
Keywords | Amurensin G; Angiogenesis; Pin1; Tamoxifen-resistant breast cancer; VEGF; Vitis amurensis -------------------------------------------------------------------------------- |
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 growthfactor (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. |
ISSN | 0278-6915 |
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Registered Date |
2017-04-19 |
