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

Simon J Hogg,Ashley Garrill,Wafaa Hassan,Peter H Sykes,Kenny Chitcholtan

doi:10.1155/2015/279591

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.

Highlights

Ovarian cancer is a lethal malignancy, and the prognosis is very poor for women who present with an advanced stage of the disease [1]
In this study we investigated whether resveratrol, acetyl-resveratrol, and polydatin elicited antigrowth of 3D cell aggregates of the EGFR/Her-2 positive cell line SKOV-3 and the EGFR/Her-2 negative cell line OVCAR-8
SKOV-3 cells formed large dense aggregates with circular, oval, and tubular structures in nontreated samples (Figures 2(a), 2(f), and 2(k)). This general morphology and aggregate size were not affected by the lower concentrations (5 μM and 10 μM) of all of the tested compounds. 3D aggregates of control, low concentration treated resveratrol (Figures 2(b) and 2(c)), acetyl-resveratrol (Figures 2(g) and 2(h)), and polydatin (Figures 2(l) and 2(m)) had a smooth rim

Summary

Introduction

Ovarian cancer is a lethal malignancy, and the prognosis is very poor for women who present with an advanced stage of the disease [1]. As chemotherapy is not normally curative in women with advanced ovarian cancers, treatments that can slow the growth of tumours and, prolong the life of those with the disease are of great importance. Advanced ovarian cancer is often associated with ascites, the excess accumulation of the body fluid in the abdominal cavity [2, 3]. Ascitic fluid which can move freely around the abdominal cavity contains malignant ovarian cells; these cells can become deposited on the surface of peritoneal membrane, thereby establishing multiple sites of secondary growth. The floating cancer cells often form small 3D aggregates, which may help them to survive as they circulate in the abdominal cavity [3]. There have been limited studies that focus on the use of possible therapeutic targets in these ovarian cancer aggregates

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