Capilliposide B inhibits the migration of prostate cancer by inducing autophagy through the ROS/AMPK/mTOR pathway

Phytother Res. 2023 Jul;37(7):2902-2914. doi: 10.1002/ptr.7785. Epub 2023 Mar 3.

Abstract

Capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, is a potent anticancer agent. However, its anticancer mechanism remains elusive. In the present study, we demonstrated the potent anti-tumor activity and molecular mechanism of CPS-B both in vitro and in vivo. Proteomic analysis using isobaric tags for relative and absolute quantitation techniques suggested that CPS-B modulated autophagy in prostate cancer (PC). Moreover, Western blotting showed that both autophagy and epithelial-mesenchymal transition occurred place after CPS-B treatment in vivo, which was also proven in PC-3 cancer cells. We deduced that CPS-B inhibited migration by inducing autophagy. We examined the accumulation of reactive oxygen species (ROS) in cells, and in downstream pathways, LKB1 and AMPK were activated while mTOR was inhibited. Transwell experiment results showed that CPS-B inhibited the metastasis of PC-3 cells and that this effect was significantly attenuated after pretreatment with chloroquine, indicating that CPS-B inhibited metastasis via autophagy induction. Altogether, these data suggest that CPS-B is a potential therapeutic agent for cancer treatment that acts by inhibiting migration through the ROS/AMPK/mTOR signaling pathway.

Keywords: AMPK; autophagy; capilliposide B; mTOR; migration; prostate cancer.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Apoptosis
  • Autophagy
  • Cell Line, Tumor
  • Humans
  • Male
  • Prostatic Neoplasms* / metabolism
  • Proteomics
  • Reactive Oxygen Species / metabolism
  • Saponins* / pharmacology
  • Saponins* / therapeutic use
  • TOR Serine-Threonine Kinases / metabolism
  • Triterpenes* / pharmacology
  • Triterpenes* / therapeutic use

Substances

  • Reactive Oxygen Species
  • AMP-Activated Protein Kinases
  • capilliposide B
  • TOR Serine-Threonine Kinases
  • Saponins
  • Triterpenes