Pro- and anticarcinogenic mechanisms of piceatannol are activated dose dependently in MCF-7 breast cancer cells.
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.
Vo
Nha T P
NT
Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Madlener
Sibylle
S
Bago-Horvath
Zsuzsanna
Z
Herbacek
Irene
I
Stark
Nicole
N
Gridling
Manuela
M
Probst
Paul
P
Giessrigl
Benedikt
B
Bauer
Sabine
S
Vonach
Caroline
C
Saiko
Philipp
P
Grusch
Michael
M
Szekeres
Thomas
T
Fritzer-Szekeres
Monika
M
Jäger
Walter
W
Krupitza
Georg
G
Soleiman
Afschin
A
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000517:prevention & control*; D016466:CHO Cells; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D016259:Genes, myc; D006801:Humans; D011960:Receptors, Estrogen / Q000502:physiology; D011980:Receptors, Progesterone / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology* / Q000633:toxicity*; D014920:Wine
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D048049:Extracellular Signal-Regulated MAP Kinases