Abstract
Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance.
| Original language | English |
|---|---|
| Pages (from-to) | 1078-1087 |
| Number of pages | 10 |
| Journal | Molecular BioSystems |
| Volume | 8 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Mar 2012 |
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ASJC Scopus subject areas
- Biotechnology
- Molecular Biology
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Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. / Vergara, Daniele; Simeone, Pasquale; Toraldo, Daniela; Del Boccio, Piero; Vergaro, Viviana; Leporatti, Stefano; Pieragostino, Damiana; Tinelli, Andrea; De Domenico, Stefania; Alberti, Saverio; Urbani, Andrea; Salzet, Michel; Santino, Angelo; Maffia, Michele.
In: Molecular BioSystems, Vol. 8, No. 4, 03.2012, p. 1078-1087.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells
AU - Vergara, Daniele
AU - Simeone, Pasquale
AU - Toraldo, Daniela
AU - Del Boccio, Piero
AU - Vergaro, Viviana
AU - Leporatti, Stefano
AU - Pieragostino, Damiana
AU - Tinelli, Andrea
AU - De Domenico, Stefania
AU - Alberti, Saverio
AU - Urbani, Andrea
AU - Salzet, Michel
AU - Santino, Angelo
AU - Maffia, Michele
PY - 2012/3
Y1 - 2012/3
N2 - Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance.
AB - Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance.
UR - http://www.scopus.com/inward/record.url?scp=84858050384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858050384&partnerID=8YFLogxK
U2 - 10.1039/c2mb05486h
DO - 10.1039/c2mb05486h
M3 - Article
C2 - 22234583
AN - SCOPUS:84858050384
VL - 8
SP - 1078
EP - 1087
JO - Molecular BioSystems
JF - Molecular BioSystems
SN - 1742-206X
IS - 4
ER -