Rotundic Acid Induces Cas3-Mcf-7 Cell Apoptosis Through The P53 Pathway
ONCOLOGY LETTERS(2019)
摘要
In the present study, the functions and mechanisms of rotundic acid (RA) underlying its induction of apoptosis in caspase-3-transfected MCF-7 human breast cancer cells (Cas3-MCF-7 cells) were investigated. RA induced apoptosis in Cas3-MCF-7 cells more efficiently compared with that in MCF-7 cells transfected with control plasmid. The results from an MTT assay demonstrated that RA effectively inhibited Cas3-MCF-7 cell viability in a dose-dependent manner and induced cell apoptosis via caspase-3 activity within 12 to 48 h. Western blotting and fluorescence-activated cell sorting demonstrated that RA initiated Cas3-MCF-7 cell apoptosis via p53 activation. The silencing of the p53 gene in the Cas3-MCF-7 cell line led to decreased RA-induced Cas3-MCF-7 cell caspase-3 activity and cell apoptosis. Collectively, the results of the present study indicate that caspase-3 serves a critical function in rotundic acid-induced apoptosis, and suggest that caspase-3 deficiency may contribute to the chemotherapy-resistance of breast cancer. Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to chemotherapy. RA has the potential for development as a novel drug combined with reconstitution of caspase-3 gene therapy for the treatment of human breast cancer with caspase-3 deficiency.
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关键词
rotundic acid,apoptosis,p53,MCF-7 cells
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