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Int J Mol Sci. 2019 Jul 2;20(13). pii: E3244. doi: 10.3390/ijms20133244.

Pro-Apoptotic Effect of Grape Seed Extract on MCF-7 Involves Transient Increase of Gap Junction Intercellular Communication and Cx43 Up-Regulation: A Mechanism of Chemoprevention.

Author information

1
National Research Council (CNR), Institute of Science of Food Production (ISPA), Unit of Lecce, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy. antonella.leone@ispa.cnr.it.
2
National Research Council (CNR), Institute of Science of Food Production (ISPA), Unit of Lecce, Via Prov.le Lecce-Monteroni, 73100 Lecce, Italy.
3
Food Department of Paediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA.

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.

KEYWORDS:

Cx43 expression; MCF-7; antioxidants; apoptosis; chemoprevention; chemotherapy; connexins; gap junction intercellular communication; grape seed Extract (GSE); nutraceuticals

PMID:
31269652
DOI:
10.3390/ijms20133244
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