Abstract
For many years, in vitro and in vivo studies have reported that organosulfur compounds (OSCs), naturally found in Allium vegetables, are able to suppress the proliferation of various tumor cells. In spite of recent advances, the specific molecular mechanisms involved in OSC activity are still unclear. Considering the antiproliferative effects observed in cancer cells, we postulated that OSCs might target the cell division cycle (Cdc) 25 phosphatases which are crucial enzymes of the cell cycle. Our findings suggest phosphatases Cdc25 as possible targets of naturally occuring polysulfides contributing to their anticancer properties. We report on the inhibitory activity of tetrasulfides occurring naturally in garlic and onion towards the human Cdc25 phosphatases. Diallyl- and dipropyltetrasulfides have emerged as interesting irreversible inhibitors of the Cdc25 isoforms A and C in vitro. Furthermore, growth of both sensitive (MCF-7) and resistant (Vcr-R) human breast carcinoma cells was significantly decreased by these tetrasulfides. The observed antiproliferative effect appeared to be associated with a G2-M cell cycle arrest.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allyl Compounds / chemical synthesis
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Allyl Compounds / pharmacology*
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / pharmacology*
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Breast Neoplasms / pathology*
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CDC2 Protein Kinase / metabolism
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cell Survival / drug effects
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Cyclin-Dependent Kinase 2 / metabolism
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Drug Resistance, Neoplasm
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Drug Screening Assays, Antitumor
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Enzyme Assays
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Female
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Garlic
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / chemistry
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Isoenzymes / isolation & purification
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Onions
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Phosphorylation
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Recombinant Proteins / antagonists & inhibitors*
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Recombinant Proteins / chemistry
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Recombinant Proteins / isolation & purification
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Sulfides / chemical synthesis
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Sulfides / pharmacology*
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cdc25 Phosphatases / antagonists & inhibitors*
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cdc25 Phosphatases / chemistry
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cdc25 Phosphatases / isolation & purification
Substances
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Allyl Compounds
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Antineoplastic Agents
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Isoenzymes
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Recombinant Proteins
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Sulfides
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dipropyl tetrasulfide
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CDC2 Protein Kinase
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CDK2 protein, human
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Cyclin-Dependent Kinase 2
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cdc25 Phosphatases
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diallyl tetrasulfide