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.
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