Sophoraflavanone G from Sophora flavescens induces apoptosis in triple-negative breast cancer cells

Phytomedicine. 2019 Aug:61:152852. doi: 10.1016/j.phymed.2019.152852. Epub 2019 Jan 29.

Abstract

Background: A compound isolated from Sophora flavescens-sophoraflavanone G (SG)-showed anti-tumor and anti-inflammatory properties. We previously demonstrated that SG promoted apoptosis in human leukemia HL-60 cells. In the present study, we investigated the effects of SG on apoptosis in human breast cancer MDA-MB-231 cells, and explored the underlying molecular mechanisms.

Methods: MDA-MB-231 cells were treated with various SG concentrations, and cell viability was evaluated by MTT assay. Apoptotic signal proteins were detected by western blotting, and cell apoptosis was assessed using flow cytometry.

Results: Our results demonstrated that SG induced nuclear condensation, DNA fragmentation, reactive oxygen species production, and increased cell apoptosis in MDA-MB-231 cells. SG also suppressed migration and invasion, likely via blockage of the MAPK pathway. In the apoptotic signaling pathway, SG increased cleaved caspase-8, caspase-3, and caspase-9. SG treatment also decreased Bcl-2 and Bcl-xL expression, increased Bax expression, and prompted release of more cytochrome c from mitochondria to the cytoplasm in MDA-MB-231 cells.

Conclusion: Overall, our findings suggest that SG might increase apoptosis, and decrease migration and invasion, in MDA-MB-231 cells through suppression of a MAPK-related pathway.

Keywords: Apoptosis; Caspase-3; MDA-MB-231 cells; Sophoraflavanone G.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Autophagy / drug effects
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Female
  • Flavanones / pharmacology*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Sophora / chemistry
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • Reactive Oxygen Species
  • Cytochromes c
  • vexibinol
  • Proto-Oncogene Proteins c-akt
  • Caspases