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

Carcinogenesis 2010 Dec 20;31(12):2074-81. Epub 2009 Aug 20.

Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgp199DOI Listing
December 2010
23 Reads

Publication Analysis

Top Keywords

pic concentrations
16
breast cancer
12
pic
10
mcf-7 breast
8
cancer cells
8
cancer cell
8
cancer
5
synthesis activated
4
inhibited deoxynucleotide
4
deoxynucleotide triphosphate
4
activated chk2
4
triphosphate synthesis
4
chk2 p38-mapk
4
inhibited activation
4
activation akt
4
akt high
4
high pic
4
apoptosis inhibited
4
growth apoptosis
4
p38-mapk accompanied
4

References

(Supplied by CrossRef)

Similar Publications