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Deoxypodophyllotoxin induces G2/M cell cycle arrest and apoptosis in SGC-7901 cells and inhibits tumor growth in vivo.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2015 Jan 20; Vol. 20 (1), pp. 1661-75. Date of Electronic Publication: 2015 Jan 20. - Publication Year :
- 2015
-
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.
- Subjects :
- Angiogenesis Inhibitors pharmacology
Animals
Antineoplastic Agents, Phytogenic pharmacology
Caspases metabolism
Cell Cycle Proteins metabolism
Cell Line, Tumor
Cell Proliferation drug effects
Drugs, Chinese Herbal
Enzyme Activation drug effects
Female
Humans
Mice, Nude
Microtubules drug effects
Microtubules metabolism
Microvessels drug effects
Microvessels pathology
Podophyllotoxin chemistry
Podophyllotoxin pharmacology
Podophyllotoxin therapeutic use
Proto-Oncogene Proteins c-bcl-2 metabolism
Stomach Neoplasms enzymology
Xenograft Model Antitumor Assays
Apoptosis drug effects
G2 Phase Cell Cycle Checkpoints drug effects
M Phase Cell Cycle Checkpoints drug effects
Podophyllotoxin analogs & derivatives
Stomach Neoplasms drug therapy
Stomach Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 25608854
- Full Text :
- https://doi.org/10.3390/molecules20011661