Abstract
Growing evidence suggests dietary antioxidants reduce the risk of several cancers. Grape seeds extracts (GSE) are a rich source of polyphenols known to have antioxidant, chemopreventive and anticancer properties. Herein, we investigated the in vitro effects and putative action mechanisms of a grape seed extract (GSE) on human breast cancer cells (MCF-7). The effects of GSE were evaluated on cell proliferation, apoptosis and gap-junction-mediated cell-cell communications (GJIC), as basal mechanism involved in the promotion stage of carcinogenesis. GSE (0.05–100 μg/mL) caused a significant dose- and time-dependent inhibition of MCF-7 viability and induced apoptotic cell death, as detected by Annexin-V/Propidium Iodide. Concurrently, GSE induced transient but significant enhancement of GJIC in non-communicating MCF-7 cells, as demonstrated by the scrape-loading/dye-transfer (SL/DT) assay and an early and dose-dependent re-localization of the connexin-43 (Cx43) proteins on plasma membranes, as assayed by immunocytochemistry. Finally, real-time-PCR has evidenced a significant increase in cx43 mRNA expression. The results support the hypothesis that the proliferation inhibition and pro-apoptotic effect of GSE against this breast cancer cell model are mediated by the GJIC improvement via re-localization of Cx43 proteins and up-regulation of cx43 gene, and provide further insight into the action mechanisms underlying the health-promoting action of dietary components.
Highlights
Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall
The antioxidant activity (AA) assayed in the hydroalcoholic extracts was higher in the grape seed (GS) extracted by methanol than ethanol (11.6 ± 0.5 and 3.3 ± 0.1 mol Trolox equivalents (TE)/100g GS), AA showed no significant differences between the extraction solvents, when Grape seeds extracts (GSE) were expressed in terms of phenolic content (7.07 ± 0.54 and 5.87 ± 0.70 mol TE/g of gallic acid equivalent (GAE) in 80% methanol and 80% ethanol, respectively)
The GSE antioxidant activity remained stable when polyphenolic extracts were solubilized in 50% acetonitrile; the AA was always equal to or greater than the AA measured in GSE solubilized in methanol
Summary
Breast cancer is the most commonly occurring cancer in women and the second most common cancer overall. There were over 2 million new cases in 2018 and the top 25 countries with the highest rates of breast cancer are in the West [1]. Environmental factors seem the major cause of breast cancer, among them are diet and lifestyle [2]. Multifactorial etiology is involved, a strong correlation between cancer and increased oxidative stress has long been established. Nutraceuticals, non-nutritive dietary components, mainly phytochemicals with antioxidant activity such as polyphenols [3], might protect against human diseases related to oxidative stress, such as hypertensive and cardiovascular diseases, and cancer. Grape components, including by-products generated during wine processing as grape seeds, are rich sources of polyphenols [3,4,5,6,7,8,9]
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