1. Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells
- Author
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Guan Wang, Lei Wang, Jian Huang, Guo-Yu Li, Dejuan Sun, Ke Zhang, Lixia Chen, Jin Zhang, Yingnan Jiang, and Suyu Gao
- Subjects
Models, Molecular ,0301 basic medicine ,MAPK/ERK pathway ,Programmed cell death ,p38 mitogen-activated protein kinases ,Apoptosis ,Biochemistry ,Structure-Activity Relationship ,03 medical and health sciences ,Chalcones ,0302 clinical medicine ,Euphorbia ,Drug Discovery ,Autophagy ,Tumor Cells, Cultured ,Humans ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Chemistry ,Cytochrome c ,Organic Chemistry ,Antineoplastic Agents, Phytogenic ,Cell biology ,030104 developmental biology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,biology.protein ,Drug Screening Assays, Antitumor - Abstract
Five flavones, including four flavonoids and one prenylated chalcone (paratocarpin E), were isolated from E. humifusa. and their chemical structures were established by spectroscopic analyses. We assessed the efficacy of these compounds against the growth of human breast cancer, leukemic, kidney cancer cell lines. Among them, paratocarpin E showed significant cytotoxicity against these cancer cell lines with an IC50 of 19.6μM on the growth of MCF-7 cells. Paratocarpin E treatment of MCF-7 cells resulted in typical apoptotic features via increasing expression of activated caspase-8 and -9 and PARP cleavage. Moreover, paratocarpin E altered the expression of Bax and Bcl-2, leading to the release of cytochrome c from the mitochondria into the cytosol, suggesting that the mitochondria-mediated apoptosis was initiated. In addition, paratocarpin E increased the MDC-positive autophagic vacuoles, the ratio of LC3-II/LC3-I protein levels of Beclin-1, but decreased p62 expression, indicating the potent pro-autophagic effects of paratocarpin E in MCF-7 cells. Mechanistically, cell death induced by paratocarpin E is able to induce apoptosis of MCF-7 cells by activating p38 and JNK signaling pathway while inhibiting Erk pathway. Furthermore, paratocarpin E promotes the activation and nuclear translocation of NF-κB, which plays an important role in balancing paratocarpin E-mediated apoptosis and autophagy. The molecular docking study also revealed that paratocarpin E bound to Fas and NF-κB complex. These findings provide initial evidences that paratocarpin E can be used as a potential anti-cancer drug in future for breast cancer therapy.
- Published
- 2016