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Actein Inhibits Tumor Growth and Metastasis in HER2-Positive Breast Tumor Bearing Mice via Suppressing AKT/mTOR and

Xiao-Xiao Wu1,2, Grace Gar-Lee Yue2,3, Jin-Run Dong4

  • 1Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China.

Frontiers in Oncology
|June 18, 2020
PubMed

Insights

Actein, a natural compound, effectively inhibits HER2-positive breast cancer cell growth and metastasis. This study highlights actein

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • HER2-positive breast cancer is aggressive, with high rates of central nervous system (CNS) metastasis.
  • CNS progression significantly impacts survival in metastatic HER2-positive breast cancer patients.

Purpose of the Study:

  • To investigate the anti-metastatic potential of actein, a natural cycloartane triterpene.
  • To elucidate the mechanisms underlying actein's effects on HER2-positive breast cancer cells and metastasis.

Main Methods:

  • In vitro studies on HER2-positive breast cancer cells (MDA-MB-361) assessing adhesion, migration, proliferation, and matrix degradation.
  • Analysis of cell cycle (G1 arrest) and key protein expressions (cyclins, CDKs, AKT/mTOR, Ras/Raf/MAPK pathways).
  • In vivo studies using tumor-bearing mice models to evaluate anti-tumor, anti-metastatic, and anti-brain metastasis effects.

Main Results:

  • Actein significantly inhibited HER2-positive breast cancer cell viability, proliferation, and migration.
  • Actein induced G1 phase arrest and downregulated cyclins, cyclin-dependent kinases, and signaling pathways (AKT/mTOR, Ras/Raf/MAPK).
  • Actein demonstrated anti-tumor and anti-metastatic activity in vivo, including a reduction in brain metastasis.

Conclusions:

  • Actein exhibits potent anti-proliferative and anti-migratory effects on HER2-positive breast cancer cells.
  • Actein's mechanisms involve cell cycle arrest and inhibition of critical signaling pathways.
  • Actein shows promise as a potential anti-metastatic therapeutic agent for HER2-positive breast cancer, particularly for preventing brain metastasis.
Keywords:
HER2-positive breast canceracteinbrain-metastasishuman epidermal growth factor receptor 2 (HER2)metastasis

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