251. N6-isopentenyladenosine: a potential therapeutic agent for a variety of epithelial cancers.
- Author
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Spinola M, Colombo F, Falvella FS, and Dragani TA
- Subjects
- Antineoplastic Agents therapeutic use, Apoptosis drug effects, Blotting, Western, Caspase 3 metabolism, Caspase 7 metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Cell Shape drug effects, DNA, Neoplasm biosynthesis, Dose-Response Relationship, Drug, Epithelial Cells metabolism, Epithelial Cells pathology, Geranyltranstransferase metabolism, HT29 Cells, Humans, Isopentenyladenosine therapeutic use, Neoplasms drug therapy, Neoplasms metabolism, Neoplasms pathology, Time Factors, Tumor Stem Cell Assay, Antineoplastic Agents pharmacology, Epithelial Cells drug effects, Isopentenyladenosine pharmacology
- 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.
- Published
- 2007
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