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ERα down-regulation plays a key role in silibinin-induced autophagy and apoptosis in human breast cancer MCF-7 cells.
- Source :
-
Journal of pharmacological sciences [J Pharmacol Sci] 2015 Jul; Vol. 128 (3), pp. 97-107. Date of Electronic Publication: 2015 May 12. - Publication Year :
- 2015
-
Abstract
- The estrogen receptor alpha (ERα) has been proven to be one of the most important therapeutic targets in breast cancer over the last 30 years. Previous studies pointed out that a natural flavonoid, silibinin, induced apoptosis in human breast cancer MCF-7 cells. In the present study we report that exposure of MCF-7 cells to silibinin led to cell death through the down-regulation of ERα expression. Silibinin-induced apoptosis of MCF-7 cells through up-regulation of caspase 6 due to ERα signalling repression was further boosted by ERα antagonist. Moreover, up-regulation of autophagy induced by silibinin accounted for apoptotic exacerbation, being further enhanced by ERα inhibition. Upon ERα activation, series of downstream signalling pathways can be activated. We found that silibinin reduced the expressions of Akt/mTOR and extracellular-signal-related kinase (ERK), which respectively accounted for the induction of autophagy and apoptosis. These effects were further augmented by co-treatment with ERα inhibitor. We conclude that the treatment with silibinin of ERα-positive MCF-7 cells down-regulates the expression of ERα, and subsequently mTOR and ERK signaling pathways, ERα downstream, finally resulting in induction of autophagy and apoptosis.<br /> (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)
- Subjects :
- Female
Humans
MAP Kinase Signaling System genetics
MAP Kinase Signaling System physiology
MCF-7 Cells
Silybin
TOR Serine-Threonine Kinases genetics
TOR Serine-Threonine Kinases metabolism
Apoptosis drug effects
Apoptosis genetics
Autophagy drug effects
Autophagy genetics
Breast Neoplasms genetics
Breast Neoplasms pathology
Down-Regulation drug effects
Down-Regulation genetics
Estrogen Receptor alpha physiology
Gene Expression drug effects
Gene Expression genetics
Silymarin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1347-8648
- Volume :
- 128
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 26117209
- Full Text :
- https://doi.org/10.1016/j.jphs.2015.05.001