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
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis / drug effects*
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Caspases / metabolism
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Cell Cycle Proteins / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drugs, Chinese Herbal
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Enzyme Activation / drug effects
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Female
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G2 Phase Cell Cycle Checkpoints / drug effects*
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Humans
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M Phase Cell Cycle Checkpoints / drug effects*
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Mice, Nude
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Microtubules / drug effects
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Microtubules / metabolism
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Microvessels / drug effects
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Microvessels / pathology
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Podophyllotoxin / analogs & derivatives*
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Podophyllotoxin / chemistry
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Podophyllotoxin / pharmacology
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Podophyllotoxin / therapeutic use
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Stomach Neoplasms / drug therapy*
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Stomach Neoplasms / enzymology
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Stomach Neoplasms / pathology*
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Xenograft Model Antitumor Assays
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents, Phytogenic
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Cell Cycle Proteins
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Drugs, Chinese Herbal
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Proto-Oncogene Proteins c-bcl-2
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deoxypodophyllotoxin
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Caspases
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Podophyllotoxin