Journal Article

Pro- and anticarcinogenic mechanisms of piceatannol are activated dose dependently in MCF-7 breast cancer cells

Nha T.P. Vo, Sibylle Madlener, Zsuzsanna Bago-Horvath, Irene Herbacek, Nicole Stark, Manuela Gridling, Paul Probst, Benedikt Giessrigl, Sabine Bauer, Caroline Vonach, Philipp Saiko, Michael Grusch, Thomas Szekeres, Monika Fritzer-Szekeres, Walter Jäger, Georg Krupitza and Afschin Soleiman

in Carcinogenesis

Volume 31, issue 12, pages 2074-2081
Published in print December 2010 | ISSN: 0143-3334
Published online August 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp199
Pro- and anticarcinogenic mechanisms of piceatannol are activated dose dependently in MCF-7 breast cancer cells

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Estrogenic procarcinogenic effects of piceatannol (PIC) contrast reports about anticarcinogenic activities of PIC. To explain this contradiction, we investigated PIC in estrogen-dependent MCF-7 breast cancer cells and elucidated those cellular mechanisms that correlated with the observed cell effects induced by PIC. Low PIC concentrations (50 nM) induced c-Myc that depended on progesterone receptor (PR) and estrogen receptor (ER). PR-mediated c-Myc induction by PIC was independent of nuclear PR activity but depended on mitogen-activated protein kinase (MAPK) signaling and was associated with an acceleration of cancer cell proliferation. In contrast, 25 μM PIC inhibited deoxynucleotide triphosphate synthesis, activated Chk2 and p38-MAPK and this was accompanied by an attenuation of cancer cell growth. Apoptosis was most probably inhibited due to activation of Akt; however, high PIC concentrations (>100 μM) permitted apoptosis-like cell death in consequence to disruption of orchestrated mitotic signaling. The presented results show for the first time that nanomolar PIC concentrations signal through PR and Erk1/2 and provide a mechanistic explanation why moderate wine consumption—but not other alcoholic beverages—increases the breast cancer risk in women. In contrast, higher PIC concentrations in the micromolar range are considered for adjuvant anticancer therapeutic concepts.

Journal Article.  5840 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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