Apoptosis Induction via ATM Phosphorylation, Cell Cycle Arrest, and ER Stress by Goniothalamin and Chemodrugs Combined Effects on Breast Cancer-Derived MDA-MB-231 Cells.

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  • Additional Information
    • Source:
      Publisher: Hindawi Pub. Co Country of Publication: United States NLM ID: 101600173 Publication Model: eCollection Cited Medium: Internet ISSN: 2314-6141 (Electronic) NLM ISO Abbreviation: Biomed Res Int Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Hindawi Pub. Co.
    • Subject Terms:
    • Abstract:
      Goniothalamin (GTN), a styryl-lactone, exhibits inhibitory effects on many kinds of cancer cells in vitro . The objectives of this study were to investigate the anticancer activities of GTN and molecular signaling pathways associated with cell death in human breast cancer MDA-MB-231 cell line. GTN inhibited the growth of MDA-MB-231 cells. Apoptosis was confirmed by annexin V-FITC and PI staining, and apoptotic morphology was observed by microscopy. Reduction of mitochondrial transmembrane potential and enhanced caspases activities were found in GTN-treated MDA-MB-231 cells. GTN significantly altered apoptosis-related protein expressions, including Noxa, PUMA, Bax, Bim, Bad, Bcl-2, Bcl-xL, and DIABLO, which was related to the gene expression levels. Mitochondrial calcium released to the cytosol and ER stress related proteins increased, which correlated with increases in ER stress gene expression levels. GTN induced hydrogen peroxide and superoxide anion radicals in MDA-MB-231 cells associated with cell cycle arrest in G2/M phase, which was induced by phosphorylation and ATM gene expression. Moreover, GTN had synergistic effects when combined with cyclophosphamide, 5-fluorouracil, paclitaxel, and vinblastine, and additive effect with methotrexate through caspases enzyme-acceleration. In conclusion, goniothalamin-induced MDA-MB-231 cell apoptosis occurred via intrinsic and extrinsic pathways, along with ER stress. These pathways provide new targeted drug strategies for advancements in anticancer medicine.
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    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Apoptosis Regulatory Proteins)
      0 (Pyrones)
      34W9GO6B2Z (goniothalamin)
      EC 2.7.11.1 (ATM protein, human)
      EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
      EC 3.4.22.- (Caspases)
    • Publication Date:
      Date Created: 20190102 Date Completed: 20190412 Latest Revision: 20200225
    • Publication Date:
      20240105
    • Accession Number:
      PMC6287143
    • Accession Number:
      10.1155/2018/7049053
    • Accession Number:
      30598998