Scutellarin Inhibits Proliferation, Invasion, and Tumorigenicity in Human Breast Cancer Cells by Regulating HIPPO-YAP Signaling Pathway

Med Sci Monit. 2017 Oct 28:23:5130-5138. doi: 10.12659/msm.904492.

Abstract

BACKGROUND The present study aimed to investigate the effects of Scutellarin on proliferation, invasion and tumorigenicity in human breast carcinoma MCF-7 cells and its associated molecular mechanisms. MATERIAL AND METHODS The MCF-7 cells were cultured with varies of concentrations of Scutellarin in vitro. The proliferation, invasion, and apoptosis of MCF-7 cells were studied via CCK-8 assay, transwell assay, and flow cytometry. In vivo expression of the HIPPO pathway key proteins YAP and p-YAP of MCF-7 cells were analyzed by immunohistochemistry. RESULTS The inhibition rates of Scutellarin-treated MCF-7 cells were 40.1%, 58.7%, and 70.6% for 24, 48, and 72 h, respectively. The MCF-7 cell proliferation was significantly inhibited by Scutellarin. Treating MCF-7 cells with Scutellarin led to invasion inhibition. The rates apoptotic cells were between 12.4±1.9% and 23.9±2.1% in 40-120 µM Scutellarin-administrated groups, which had a significant rise compared with the control group (7.8±1.9%, P<0.05). Scutellarin significantly inhibited MCF-7 xenograft tumor growth. Immunohistochemical analysis showed that the inhibition of tumor growth in Scutellarin-treated mice was associated with increased p-YAP and decreased YAP expression in vivo. CONCLUSIONS Scutellarin-treated breast carcinoma MCF-7 cells had significantly inhibited growth and induced apoptosis, which is associated with induction of autophagy through regulation of the HIPPO-YAP signaling pathway, providing support to the clinical use of Scutellarin-based medication to achieve optimized outcome in patients with breast carcinoma.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apigenin / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinogenesis / drug effects
  • Carcinogenesis / pathology*
  • Cell Proliferation / drug effects
  • Female
  • Glucuronates / pharmacology*
  • Hippo Signaling Pathway
  • Humans
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Phosphoproteins / metabolism*
  • Phosphorylation / drug effects
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction / drug effects*
  • Transcription Factors
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Glucuronates
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • scutellarin
  • Apigenin
  • Protein Serine-Threonine Kinases