Bufalin inhibits TGF-β-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-β receptors

Int J Mol Med. 2015 Sep;36(3):645-52. doi: 10.3892/ijmm.2015.2268. Epub 2015 Jun 30.

Abstract

The epithelial-to-mesenchymal transition (EMT) is a well-known prerequisite for cancer cells to acquire the migratory and invasive capacity, and to subsequently metastasize. Bufalin is one of the major active components of the traditional Chinese medicine Chan Su, and accumulating evidence has shown its anticancer effect in multipe types of cancer. However, the role of bufalin in transforming growth factor‑β (TGF‑β)‑induced EMT and migration remains unclear. In the present study, the effect of bufalin on TGF‑β‑induced EMT and migration was investigated in human lung cancer A549 cells. TGF‑β induced EMT in A549 cells and increased their migratory ability, which were markedly suppressed by bufalin. Additionally, TGF‑β‑induced upregulation of Twist2 and zinc finger E‑box binding homeobox 2 (ZEB2), as well as the phosphorylation of Smad2 and Smad3 were also inhibited by bufalin. However, the Smad‑independent signaling pathways were not affected. Further analysis showed that the TGF‑β receptor I (TβRI) and TGF‑β receptor II (TβRII) were downregulated in the presence of bufalin. Pretreatment with SB431542, a potent inhibitor of the phosphorylation of TβRI, significantly attenuated TGF‑β‑induced EMT, mimicking the effect of bufalin on A549 cells. Taken together, these results suggest that bufalin suppresses TGF-β-induced EMT and migration by downregulating TβRI and TβRII in A549 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Bufanolides / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / metabolism*

Substances

  • Antineoplastic Agents
  • Bufanolides
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • chan su
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • bufalin