Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

Thorac Cancer. 2019 Mar;10(3):492-500. doi: 10.1111/1759-7714.12962. Epub 2019 Jan 21.


Background: Scutellarin (SCU), a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz., increases autophagy and apoptosis in the adenocarcinoma A549 cell line, which is resistant to cisplatin. However, whether SCU alone has antitumor activity against non-small cell lung cancer (NSCLC) is unknown.

Methods: Cell Counting Kit-8, flow cytometry, colony formation, Hoechst 33258 staining, and Western blot analyses were used to examine the proliferation and apoptosis of A549 cells treated with SCU and the possible molecular mechanisms.

Results: The cell viability assay indicated that SCU markedly suppressed the proliferation of A549 cells in concentration and time-dependent manners. SCU caused significant G0/G1 phase arrest and apoptosis, as evidenced by flow cytometric analyses, Hoechst 33258 staining, and Western blot analyses of cyclin D1, cyclin E, BCL-2, cleaved-caspase-3, and BAX. Furthermore, SCU treatment reduced the level of pan-AKT, phosphorylated (p)-mTOR, mTOR, BCL-XL, STAT3, and p-STAT3, and increased the level of 4EBP1.

Conclusions: SCU can suppress proliferation and promote apoptosis in A549 cells through AKT/mTOR/4EBP1 and STAT3 pathways. This suggests that SCU may be developed into a promising antitumor agent for treating NSCLC.

Keywords: Apoptosis; STAT3; cell cycle arrest; non-small cell lung cancer; scutellarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Apigenin / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / drug effects
  • Glucuronates / pharmacology*
  • Humans
  • Proto-Oncogene Proteins c-akt / genetics
  • STAT3 Transcription Factor / genetics*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / genetics


  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Glucuronates
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • scutellarin
  • Apigenin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases