Periplocin inhibits the growth of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling

Cancer Med. 2021 Jan;10(1):325-336. doi: 10.1002/cam4.3611. Epub 2020 Nov 24.

Abstract

Background: Periplocin is a monomeric compound that exhibits anti-tumor activities. It is extracted from Cortex Periplocae.

Objective: This study aimed at determining the effect of periplocin treatment on the apoptosis and proliferation of human pancreatic cancer cells, and to elucidate on its mechanisms of action.

Methods: PANC1 and cfpac1 cells were treated with periplocin. Cell proliferation was detected by RTCA, Ki67 immunofluorescence, and a clonogenic assay. The transwell assay was used to examine cell migration and invasion functions. The expression of apoptosis-associated proteins was detected by flow cytometry and western blotting. Total RNA was extracted from the treated and untreated group of PANC1 cells for RNA-seq detection and analysis. Differentially expressed genes were screened for GO biological process and KEGG pathway analysis. Finally, CFPAC1 cells were subcutaneously inoculated into BALB / c nude mice to assess tumor growth.

Results: Periplocin inhibited the proliferation of PANC1 and CFPAC1 cells and induced their apoptosis by activating the AMPK/mTOR pathway and inhibiting p70 S6K. It also attenuated the cell migration, invasion, and inhibited the growth of cfpac1 xenografts in nude mice.

Conclusions: Periplocin inhibits human pancreatic cancer cell proliferation and induces their apoptosis by activating the AMPK / mTOR pathway.

Keywords: Periplocin; apoptosis; pancreatic cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Saponins / pharmacology*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Saponins
  • periplocin
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases