N6-isopentenyladenosine: a potential therapeutic agent for a variety of epithelial cancers.
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.
Spinola
Monica
M
Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Colombo
Francesca
F
Falvella
F Stefania
FS
Dragani
Tommaso A
TA
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051228:Geranyltranstransferase / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007541:Isopentenyladenosine / Q000494:pharmacology* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007541:Isopentenyladenosine; D051228:Geranyltranstransferase; D053148:Caspase 3; D053179:Caspase 7