INVOLVEMENT OF POLYAMINES IN SELENOMETHIONINE INDUCED APOPTOSIS AND MITOTIC ALTERATIONS IN HUMAN TUMOR-CELLS

The efficacy of dietary selenium supplementation is currently being ev aluated in intervention trials. However, the biological mechanisms und erlying the cancer chemopreventive effects of selenium supplementation have yet to be elucidated, Selenium metabolism and polyamine biosynth esis are linked in their common requirement for S-adenosylmethionine. Selenomethionine was the predominant form of selenium in the dietary s upplement, therefore we evaluated the anti-tumorigenic effects of sele nomethionine. We found that selenomethionine inhibited tumor growth (b oth in A549 lung and HT29 colon cancer cells) in a dose-dependent mann er, At 24 and 72 h, polyamine content of A549 and HT29 cancer cell lin es was decreased at doses that inhibited 50% of normal growth, Selenom ethionine treatment induced apoptosis in both cancer cell lines, Exoge nous spermine administration, which replenishes intracellular polyamin e levels, prevented selenomethionine induced apoptosis, Selenomethioni ne administration to the cancer cell lines increased the number of cel ls in metaphase, This cell cycle effect appeared to be reversed with t he co-administration of selenomethionine and spermine, These data sugg ested that at least part of the anti-carcinogenic effects of selenium supplementation might be due to a depletion in polyamine levels, This depletion of polyamines leads to an induction in apoptosis and perturb ations in the cell cycle.