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

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.

• Authors: Yu-Rong Wang, Yuan Xu, Zhen-Zhou Jiang, Mounia Guerram, Bin Wang, Xiong Zhu, Lu-Yong Zhang
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 20 Issue 1 Pg. 1661-75 (Jan 20 2015) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 25608854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, metabolism)
• Microvessels (drug effects, pathology)
• Podophyllotoxin (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Stomach Neoplasms (drug therapy, enzymology, pathology)
• Xenograft Model Antitumor Assays