Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways

Naunyn Schmiedebergs Arch Pharmacol. 2019 May;392(5):593-603. doi: 10.1007/s00210-019-01614-5. Epub 2019 Feb 6.


Inflammation is one of the characteristic features during the development of human tumors. A pro-inflammatory cytokine that is known to promote inflammation during cancer development is the transforming growth factor-β (TGF-β). On the other hand, demethylzeylasteral (T-96) is a natural compound isolated from Tripterygium wilfordii Hook F, which has been reported to have various pharmacological properties including anti-inflammatory and immunosuppressive activities. We investigated the effects of T-96 on the highly metastatic breast cancer cell line, MDA-MB-231. Cell migration was assessed by scratch-wound migration assay, and the molecular mechanisms underlying the effects of T-96 were examined by qPCR and Western blot analyses. We also investigated the suppression effects of T-96 on the pulmonary metastasis in the 4T1 mouse model. T-96 inhibited TGF-β-induced migration and epithelial-mesenchymal transition both in vitro and in vivo. These results demonstrate that T-96 inhibited invasion of MDA-MB-231 and 4T1 cells via suppressing the canonical and non-canonical TGF-β signaling pathways.

Keywords: Breast cancer; Invasion; T-96; TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / secondary
  • Mice, Inbred BALB C
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta1 / antagonists & inhibitors*
  • Transforming Growth Factor beta1 / metabolism
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use*


  • Antineoplastic Agents
  • Transforming Growth Factor beta1
  • Triterpenes
  • demethylzeylasteral