1. Academic Validation
  2. Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment

Silibinin-induced apoptosis of breast cancer cells involves mitochondrial impairment

  • Arch Biochem Biophys. 2019 Aug 15;671:42-51. doi: 10.1016/j.abb.2019.05.009.
Lingling Si 1 Weiwei Liu 1 Toshihiko Hayashi 2 Yachao Ji 1 Jianing Fu 1 Yuheng Nie 1 Kazunori Mizuno 3 Shunji Hattori 3 Satoshi Onodera 4 Takashi Ikejima 5
Affiliations

Affiliations

  • 1 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China.
  • 2 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China; Department of Chemistry and Life Science, School of Advanced Engineering, Kogakuin University, 2665-1, Nakanomachi, Hachioji, Tokyo, 192-0015, Japan.
  • 3 Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017, Japan.
  • 4 Medical Research Institute of Curing Mibyo, 1-6-28 Narusedai Mechida Tokyo, 194-0042, Japan.
  • 5 Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China; Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, PR China. Electronic address: [email protected].
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.

Keywords

Apoptosis; Mitochondria; Mitochondrial biogenesis; Mitochondrial dynamics; Mitochondrial fragmentation; Silibinin.

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