Resveratrol, Acetyl-Resveratrol, and Polydatin Exhibit Antigrowth Activity against 3D Cell Aggregates of the SKOV-3 and OVCAR-8 Ovarian Cancer Cell Lines

Abstract

Resveratrol has aroused significant scientific interest as it has been claimed that it exhibits a spectrum of health benefits. These include effects as an anti-inflammatory and an antitumour compound. The purpose of this study was to investigate and compare any potential antigrowth effects of resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, on 3D cell aggregates of the EGFR/Her-2 positive and negative ovarian cancer cell lines SKOV-3 and OVCAR-8, respectively. Results showed that resveratrol and acetyl-resveratrol reduced cell growth in the SKOV-3 and OVCAR-8 in a dose-dependant manner. The growth reduction was mediated by the induction of apoptosis via the cleavage of poly(ADP-ribose) polymerase (PARP-1). At lower concentrations, 5 and 10 µM, resveratrol, acetyl-resveratrol, and polydatin were less effective than higher concentrations, 50 and 100 µM. In SKOV-3 line, at higher concentrations, resveratrol and polydatin significantly reduced the phosphorylation of Her-2 and EGFR and the expression of Erk. Acetyl-resveratrol, on the other hand, did not change the activation of Her-2 and EGFR. Resveratrol, acetyl-resveratrol, and polydatin suppressed the secretion of VEGF in a dose-dependant fashion. In the OVCAR-8 cell line, resveratrol and acetyl-resveratrol at 5 and 10 µM increased the activation of Erk. Above these concentrations they decreased activation. Polydatin did not produce this effect. This study demonstrates that resveratrol and its derivatives may inhibit growth of 3D cell aggregates of ovarian cancer cell lines via different signalling molecules. Resveratrol and its derivatives, therefore, warrant further in vivo evaluation to assess their potential clinical utility.

Resveratrol and acetyl-resveratrol modulate activity of VEGF and IL-8 in ovarian cancer cell aggregates via attenuation of the NF-κB protein

“…It has been previously shown that resveratrol reduces the growth of monolayer and clusters of ovarian cancer cell lines [32]. We further examined this in 3D cell aggregates using concentrations of resveratrol and acetyl-resveratrol that were closer to levels found in human serum [29], using the Alamar blue dye assay (Fig.…”

“…We used a 10 μM dose as this concentration can be found in food products and is pharmacologically relevant [29]. Previously we have tested 5, 10, 50 and 100 μM resveratrol and acetyl resveratrol [32] and found that 50 and 100 μM of both compounds was able to reduce cell growth and increase cleaved PARP protein. Therefore, we chose to investigate 20 μM and 30 μM as they are in between the pharmacologically relevant dose and the previously established effective dose.…”

Anticancer Molecular Mechanisms of Resveratrol

“…EGF-R promotes cell growth and proliferation, and it is typically over-expressed in aggressive tumor phenotypes ( 16 ). Acting on EGF-R pathway, resveratrol and two of its derivatives, acetyl-resveratrol and polydatin, displayed the dose-dependent antigrowth effects against 3D cell aggregates of the EGF-R/Her-2-positive and -negative ovarian cancer cell lines, although via different signaling molecules ( 17 ). When tested on the positive ovarian cell line and at high concentrations, in particular, resveratrol and polydatin (but not acetyl-resveratrol) significantly reduced the phosphorylation of Her-2 and EGF-R, and decreased the expression of extracellular-signal-regulated kinases (ERK) and vascular endothelial growth factor (VEGF) ( 17 ).…”

Uncovering the action mechanism of polydatinvianetwork pharmacological target prediction

“…26,27 In vitro experimental assays revealed that PD could reduce the phosphorylation of EGFR in ovarian cancer cell lines. 28 Moreover, Caspase-3 (CASP3), as a member of Caspases, is an executioner that implements apoptosis. 29,30 It mediates apoptosis by destroying a series of cellular substrates, and activates the degradation of DNA.…”