Halofuginone-induced autophagy suppresses the migration and invasion of MCF-7 cells via regulation of STMN1 and p53

J Cell Biochem. 2018 May;119(5):4009-4020. doi: 10.1002/jcb.26559. Epub 2018 Jan 19.

Abstract

Traditional Chinese medicines have been recognized as especially promising anticancer agents in modern anticancer research. Halofuginone (HF), an analog of quinazolinone alkaloid extracted from Dichroa febrifuga, is widely used in traditional medicine. However, whether HF inhibits the growth of breast cancer cells and/or reduces the migration and invasion of MCF-7 human breast cancer cells, as well as the underlying mechanisms in vitro, remains unclear. In this study, we report that an HF extract inhibits the growth of MCF-7 cells and reduces their migration and invasion, an important feature of potential anticancer agents. In addition, HF significantly increases the activation of autophagy, which is closely associated with tumor metastasis. As STMN1 and p53 have been closely implicated in breast cancer progression, we analyzed their expression in the context of HF extract treatment. Western blot analysis showed that HF suppresses STMN1 and p53 expression and activity in an autophagy-dependent manner. Collectively, these data indicate that activation of autophagy reduces expression of STMN1 and p53, and the migration and invasion of cancer cells contributes to the anti-cancer effects of the HF. These findings may provide new insight into breast cancer prevention and therapy.

Keywords: Halofuginone; MCF-7; STMN1; autophagy; migration and invasion; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement
  • Female
  • Humans
  • MCF-7 Cells
  • Neoplasm Invasiveness
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Stathmin / biosynthesis*
  • Tumor Suppressor Protein p53 / biosynthesis*

Substances

  • Piperidines
  • Quinazolinones
  • STMN1 protein, human
  • Stathmin
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • halofuginone