Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901 cells and inhibits tumor growth in vivo

Molecules. 2015 Jan 20;20(1):1661-75. doi: 10.3390/molecules20011661.

Abstract

Deoxypodophyllotoxin (DPT), a natural microtubule destabilizer, was isolated from Anthriscus sylvestris, and a few studies have reported its anti-cancer effect. However, the in vivo antitumor efficacy of DPT is currently indeterminate. In this study, we investigated the anti-gastric cancer effects of DPT both in vitro and in vivo. Our data showed that DPT inhibited cancer cell proliferation and induced G2/M cell cycle arrest accompanied by an increase in apoptotic cell death in SGC-7901 cancer cells. In addition, DPT caused cyclin B1, Cdc2 and Cdc25C to accumulate, decreased the expression of Bcl-2 and activated caspase-3 and PARP, suggesting that caspase-mediated pathways were involved in DPT-induced apoptosis. Animal studies revealed that DPT significantly inhibited tumor growth and decreased microvessel density (MVD) in a xenograft model of gastric cancer. Taken together, our findings provide a framework for further exploration of DPT as a novel chemotherapeutic for human gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drugs, Chinese Herbal
  • Enzyme Activation / drug effects
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects*
  • Mice, Nude
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Microvessels / drug effects
  • Microvessels / pathology
  • Podophyllotoxin / analogs & derivatives*
  • Podophyllotoxin / chemistry
  • Podophyllotoxin / pharmacology
  • Podophyllotoxin / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Cell Cycle Proteins
  • Drugs, Chinese Herbal
  • Proto-Oncogene Proteins c-bcl-2
  • deoxypodophyllotoxin
  • Caspases
  • Podophyllotoxin