Toxicarioside N induces apoptosis in human gastric cancer SGC-7901 cell by activating the p38MAPK pathway

Arch Pharm Res. 2018 Jan;41(1):71-78. doi: 10.1007/s12272-017-0956-4. Epub 2017 Sep 22.

Abstract

Natural plant compounds with potent proliferation inhibition and apoptosis induction properties have been screened as novel anticancer drugs. Toxicarioside N (Tox N) was isolated from the seeds of the tropical plant Antiaris toxicaria in Hainan province, China. To our knowledge, the effects that Tox N has on the apoptosis of SGC-7901 cells and its potential mechanism have never been investigated. In this study, we detected the anticancer activities of Tox N and explored the potential mechanism in the human gastrointestinal cancer cell line SGC-7901. Here, we found that Tox N inhibited SGC-7901 cell growth in a dose- and time-dependent manner and induced apoptosis in cells based on cell morphology and flow cytometry analyses. Additionally, the SGC-7901 cell treated with Tox N up-regulated the expression level of cleaved caspase-3/9 and PARP, increased the Bax/Bcl-2 ratio, and led to the release of cytochrome c into the cytoplasm. In addition, Tox N treatment led to the phosphorylation of p38MAPK. SB203580, a p38MAPK inhibitor, partially attenuated Tox N induced apoptosis by preventing the activation of caspase-3/9 and PARP. Our results indicated for the first time that Tox N can induce SGC-7901 cells apoptosis by activating the p38MAPK pathway.

Keywords: Apoptosis; SGC-7901 cells; Toxicarioside N; p38MAPK.

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Glycosides / chemistry
  • Glycosides / isolation & purification
  • Glycosides / pharmacology*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Molecular Conformation
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Glycosides
  • toxicarioside N
  • p38 Mitogen-Activated Protein Kinases