Elsevier

Toxicology Letters

Volume 230, Issue 2, 15 October 2014, Pages 218-224
Toxicology Letters

Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells

https://doi.org/10.1016/j.toxlet.2014.01.042Get rights and content

Abstract

A major part of the wineries’ wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts’ use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC50 values of 121–230 μg/ml (MCF-7), 121–184 μg/ml (MDA-MD-23), 175–309 μg/ml (HT29), 159–314 μg/ml (K1), 180–225 μg/ml (786-0) and 134–>400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.

Introduction

Vitis vinifera (grape) comprises one of the world's largest crops and along with its basic product, wine, has been part of the human diet since antiquity. Apart from their economic value, during the last years grape and wine were extensively studied due to their significant biological properties (Mullin, 2011). It must be pointed out that a broad variety of food supplements referred to as ‘grape seed extracts’ is consumed worldwide for their beneficial properties on human health. Our research group has demonstrated previously that grape extracts exhibit strong antioxidant activities and prevent the DNA damage induced by reactive oxygen species (ROS) (Stagos et al., 2005, Stagos et al., 2006). Moreover, grape extracts have been reported to inhibit human cancer cell growth (Shrotriya et al., 2012) and tumor growth in various animal models (Sun et al., 2012). The molecular mechanisms involved in the anti-carcinogenic activities of grape extracts include the induction of apoptosis through modulation of cell signaling and cell-cycle regulators (Agarwal et al., 2000a), inhibition of enzymes playing an essential role in cell proliferation (e.g. human topoisomerase I) (Stagos et al., 2005) and inhibition of angiogenesis (Agarwal et al., 2004).

However, the wineries’ wastes are harmful for the environment due to their high organic load and high acidity attributing mainly to their polyphenolic content. For this reason, most of the wine-producing countries as well as other institutions (e.g. European Union) have established regulations for the proper management of the winery's waste. A major part (3–5% of the processed grapes) of the solid wastes of wineries is composed of grape stems. Currently, a small portion of grape stems is used as animal feed and/or in the production of natural organic fertilizers (compost), processes of limited economical interest (Arvanitoyannis et al., 2006), while the majority, along with other wastes of the wine making process, is discarded in nearby open fields. The environmental problems faced introduce the need for the development of method for their proper management via utilization.

Interestingly, one of our previous studies has shown that grape stem extracts are rich in bioactive polyphenols such as flavonoids, stilbenes and phenolic acids, suggesting their potential use as a source of high added value polyphenols, an activity that would combine the profitable venture with the environmental protection in wine-producing zones (Anastasiadi et al., 2009). Moreover, we have recently shown that grape stem extracts display significant antioxidant activity, protective activity against ROS-induced DNA damage and inhibitory activity against human hepatocellular and cervical cancer cells (Apostolou et al., 2014).

Having in mind the well established anticancer properties of grape stem extracts against liver and cervical cancer cells, this endeavor aims to extend these studies in order to investigate the inhibitory effects of the extracts against the growth of additional human cancer cell types such as breast, renal, thyroid and colon.

Section snippets

Chemicals and reagents

Gallic acid, (+)-catechin, (−)-epicatechin, p-coumaric acid, ferulic acid, caffeic acid, syringic acid, kaempferol, quercetin, rutin and trans-resveratrol were purchased from Sigma–Aldrich (Steinheim, Germany). The Folin–Ciocalteu reagent was purchased from Fluka (Steinheim, Germany). All solvents used for the qualitative and quantitative determination of polyphenols were purchased from J. T. Baker (Griesheim, Germany) as analytical (polyphenol extraction) or HPLC (chromatographic analyses)

Results and discussion

The results of the assessment of the Total Polyphenolic Content (TPC) and the polyphenolic composition of the investigated extracts are presented in Table 1. The TPC and polyphenolic composition of grape stem extract of Hambourg Muscat (2009) variety have already been published (Apostolou et al., 2014), but are included herein for the reader's convenience. The measured TPC values ranged from 318 to 415 mg GAE/g dry weight (dw) (Table 1) and are similar to those reported previously (Anastasiadi

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Transparency document

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Acknowledgments

This research has been co-financed by the European Union (European Social Fund – ESF) and Greek National Funds through the Operational Program ‘Education and Lifelong Learning’ of the National Strategic Reference Framework (NSRF) – Research Funding Program: ‘Heracleitus II. Investing in knowledge society through the European Social Fund’.

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