Scutellaria baicalensis Georgi induces caspase-dependent apoptosis via mitogen activated protein kinase activation and the generation of reactive oxygen species signaling pathways in MCF-7 breast cancer cells

Mol Med Rep. 2017 Aug;16(2):2302-2308. doi: 10.3892/mmr.2017.6798. Epub 2017 Jun 16.

Abstract

Scutellaria baicalensis Georgi extract (SBGE) is used in traditional herbal medicine and has also been used clinically to ameliorate the symptoms of various inflammatory diseases and cancer. In women, breast cancer is one of the most common diseases and numerous women succumb to it. The present study was undertaken to investigate the mechanism responsible for the SBGE‑induced apoptosis of MCF‑7 human breast cancer cells. SBGE was administered to cells at concentrations between 100 and 500 mg/ml, and cell viabilities were identified using an MTT assay. B‑cell lymphoma 2 (Bcl-2) and Bcl-2 X‑associated protein (Bax) family members were identified by western blotting, and the mRNA expression levels of the pro‑apoptosis genes Fas, Fas ligand (FasL) and tumor necrosis factor (TNF)‑α were assessed by reverse transcription‑polymerase chain reaction. It was identified that SBGE treatment for 24 h inhibited MCF‑7 proliferation and increased the sub‑G1 phase ratio. SBGE suppressed mitochondrial membrane potentials and SBGE‑induced apoptotic cell death was identified to be associated with downregulation of Bcl‑2, but upregulation of Bax. SBGE‑activated caspases 3 and 9, and increased reactive oxygen species generation. However, SBGE had no effect on the expression levels of Fas, FasL or TNF‑α. Furthermore, mitogen‑activated protein kinase and C‑Jun N‑terminal kinase inhibitors inhibited SBGE‑induced cell death. These results suggested that SBGE be considered as an agent for the treatment of breast cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / metabolism*
  • Caspase 9 / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / drug effects
  • Mitogen-Activated Protein Kinases / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Scutellaria baicalensis
  • Signal Transduction / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • Scutellaria baicalensis extract
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 9