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Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2019 Aug 15; Vol. 671, pp. 42-51. Date of Electronic Publication: 2019 May 11. - Publication Year :
- 2019
-
Abstract
- Mitochondria are dynamically regulated by fission and fusion processes. Silibinin induces apoptosis of MCF-7 and MDA-MB-231 human breast cancer cells. However, whether or not mitochondria dysfunction is involved in the apoptosis induction with silibinin of both types of the cells remains unknown. We here report that silibinin decreases the mitochondrial mass in terms of MitoTracker Green staining in both breast cancer cells. Silibinin induces morphological changes of mitochondria from oval to truncated or fragmented shapes accordingly. Condensed crests are observed in mitochondria by transmission electron microscopy. Silibinin causes mitochondrial membrane potential reduced. The expression of mitochondrial fission-associated proteins including dynamin-related protein 1 (DRP1) is up-regulated, whereas expression of the mitochondrial fusion-associated proteins, optic atrophy 1 and mitofusin 1, is down-regulated. In addition, silibinin treatment down-regulates ATP content as well as the levels of mitochondrial biogenesis-regulators including mitochondrial transcription factor A, peroxisome proliferator-activated receptor gamma coactivator 1 and nuclear respiratory factor 2. Moreover, treatments with DRP1 inhibitor, mdivi-1, or with DRP1-targetted siRNA efficiently prevent silibinin-induced apoptosis in the breast cancer cells, whereas inhibition of DRP1 phosphorylation with staurosporine increases apoptosis furthermore. Taken together, we conclude that silibinin impairs mitochondrial dynamics and biogenesis, leading to apoptosis of MCF-7 and MDA-MB-123 cells.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Cell Line, Tumor
Dynamins metabolism
GTP Phosphohydrolases metabolism
Humans
Membrane Potential, Mitochondrial drug effects
Membrane Proteins metabolism
Mitochondria pathology
Mitochondrial Dynamics drug effects
Mitochondrial Membrane Transport Proteins metabolism
Mitochondrial Proteins metabolism
Organelle Biogenesis
Quinazolinones pharmacology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Mitochondria drug effects
Silybin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 671
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 31085166
- Full Text :
- https://doi.org/10.1016/j.abb.2019.05.009