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.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Anticarcinogenic Agents/*pharmacology ; Antioxidants/*pharmacology ; Apoptosis/*drug effects ; Breast Neoplasms/*prevention & control ; Grape Seed Extract/*pharmacology; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Cell Communication/drug effects ; Connexin 43/genetics ; Connexin 43/metabolism ; Female ; Gap Junctions/drug effects ; Gap Junctions/metabolism ; Humans ; MCF-7 Cells ; Up-Regulation/drug effects
    • 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.
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    • Contributed Indexing:
      Keywords: Cx43 expression; MCF-7; antioxidants; apoptosis; chemoprevention; chemotherapy; connexins; gap junction intercellular communication; grape seed Extract (GSE); nutraceuticals
    • Accession Number:
      0 (Anticarcinogenic Agents)
      0 (Antioxidants)
      0 (Connexin 43)
      0 (GJA1 protein, human)
      0 (Grape Seed Extract)
    • Publication Date:
      Date Created: 20190705 Date Completed: 20200106 Latest Revision: 20200225
    • Publication Date:
      20240829
    • Accession Number:
      PMC6651466
    • Accession Number:
      10.3390/ijms20133244
    • Accession Number:
      31269652