NDLI: Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF-7 cells.

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Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF-7 cells.

Content Provider	Semantic Scholar
Author	Gao, Huan Zhang, Yue Dong, Lei Qu, Xiao-yu Tao, Li-Na Zhang, Yue-Ming Zhai, Jing-hui Song, Yan-qing
Copyright Year	2018
Abstract	To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF-7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF-7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl-2-associated X protein (Bax), caspase-3 and B-cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway. The results demonstrated that TPI significantly reduced the cell proliferation rate and viability in a time- and dose-dependent manner, which was confirmed by western blotting and immunofluorescent staining. TPI induced autophagy and influenced p38 mitogen-activated protein kinases, extracellular signal-regulated kinase (Erk)1/2, and mammalian target of rapamycin (mTOR) phosphorylation, which resulted in apoptosis. When cells were treated with a combination of TPI and the Erk1/2 inhibitor U0126, the downregulation of P62 and upregulation of Bax were inhibited, which demonstrated that the inhibition of Erk1/2 reversed the autophagy changes induced by TPI. The results indicated that Erk1/2 activation may be a novel mechanism by which TPI induces autophagy and apoptosis in MCF-7 breast cancer cells. In conclusion, TPI affects the proliferation and apoptosis of MCF-7 cells, potentially via autophagy and p38/Erk/mTOR phosphorylation. The present study offers a novel view of the mechanisms by which TPI regulates cell death.
Starting Page	3413
Ending Page	3419
Page Count	7
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://spandidos-publications.com/etm/15/4/3413/download
PubMed reference number	29545863v1
Alternate Webpage(s)	https://doi.org/10.3892/etm.2018.5830
DOI	10.3892/etm.2018.5830
Journal	Experimental and therapeutic medicine
Volume Number	15
Issue Number	4
Language	English
Access Restriction	Open
Subject Keyword	Apoptosis Autophagy Cascade Device Component Cell Death Cell Proliferation Cell Survival Cessation of life DCTN4 gene Down-Regulation Extracellular Signal Regulated Kinases FRAP1 protein, human Flow Cytometry Leukemia, B-Cell Mammals Mammary Neoplasms Mitogen-Activated Protein Kinases Mitogens Sirolimus TPI1 gene U 0126 Up-Regulation (Physiology) Western Blotting cancer cell caspase-3 mitogen-activated protein kinase p38 monooxyethylene trimethylolpropane tristearate triptolide
Content Type	Text
Resource Type	Article

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