Abstract
Isopentenyladenosine (i(6)A) is a product of isopentenyltransferases and, in mammals, occurs either bound to tRNA or as a free nucleoside. Sporadic reports have suggested an anticancer effect of i(6)A, mostly on leukemia cells. The present analysis of 9 human epithelial cancer cell lines derived from different types of malignant tissue revealed complete suppression of clonogenic activity in 8 of the lines after exposure to i(6)A at a concentration of 10 muM. Mechanistic studies showed that i(6)A tumor suppressor activity is associated with inhibition of cell proliferation, a block in DNA synthesis and morphological changes. These results point to i(6)A and to its possible derivatives as a new potential class of wide-spectrum anticancer agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Blotting, Western
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Caspase 3 / metabolism
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Caspase 7 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Shape / drug effects
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DNA, Neoplasm / biosynthesis
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Dose-Response Relationship, Drug
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Geranyltranstransferase / metabolism
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HT29 Cells
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Humans
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Isopentenyladenosine / pharmacology*
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Isopentenyladenosine / therapeutic use
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Neoplasms / drug therapy
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Neoplasms / metabolism
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Neoplasms / pathology
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Time Factors
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Tumor Stem Cell Assay
Substances
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Antineoplastic Agents
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DNA, Neoplasm
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Isopentenyladenosine
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Geranyltranstransferase
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Caspase 3
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Caspase 7