A natural product toosendanin inhibits epithelial-mesenchymal transition and tumor growth in pancreatic cancer via deactivating Akt/mTOR signaling

Biochem Biophys Res Commun. 2017 Nov 4;493(1):455-460. doi: 10.1016/j.bbrc.2017.08.170. Epub 2017 Sep 13.

Abstract

The pancreatic cancer is among the most aggressive malignancies with strong proclivity to metastasis. The malignancy during pancreatic cancer progression is largely ascribed to epithelial-mesenchymal transition (EMT). Here we showed that toosendanin (TSN), which is an active component in traditional Chinese medicine, can strongly attenuate pancreatic cancer progression. TSN suppressed the viability and grow of pancreatic cancer cells in a dose-dependent manner. The migration and invasion of pancreatic cancer cells were also consistently inhibited dose-dependently. TSN can reverse the TGF-β induced EMT and morphological change in pancreatic cancer cells by increasing Ecadherin expression while reducing Vimentin, ZEB1 and SNAIL levels. Furthermore, TSN evidently repressed xenograft tumor growth in mouse pancreatic cancer models without significantly toxic side effects. Mechanistic studies suggested that TSN mediated pancreatic cancer inhibition by blocking Akt/mTOR signaling pathway. Our results showed that TSN inhibits pancreatic cancer progression via downregulating Akt/mTOR signaling. Since the concentrations of TSN used in current study is very low, our results demonstrated that TSN can inhibit pancreatic cancer progression thereby implying that TSN can be used as a potential pharmacological agent especially in treatment of pancreatic cancer.

Keywords: Akt/mTOR; EMT; Pancreatic cancer; Toosendanin.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / administration & dosage*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Oncogene Protein v-akt / metabolism*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism*
  • Plant Extracts / administration & dosage*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • toosendanin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Oncogene Protein v-akt