Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells

The efficacy of dietary selenium supplementation is currently beingevaluated in intervention trials. However, the biological mechanismsunderlying the cancer chemopreventive effects of selenium supplementationhave yet to be elucidated. Selenium metabolism and polyamine biosynthesisare linked in their common requirement for S- adenosylmethionine.Selenomethionine was the predominant form of selenium in the dietarysupplement, therefore we evaluated the anti- tumorigenic effects ofselenomethionine. We found that selenomethionine inhibited tumor growth(both in A549 lung and HT29 colon cancer cells) in a dose-dependent manner.At 24 and 72 h, polyamine content of A549 and HT29 cancer cell lines wasdecreased at doses that inhibited 50% of normal growth. Selenomethioninetreatment induced apoptosis in both cancer cell lines. Exogenous spermineadministration, which replenishes intracellular polyamine levels, preventedselenomethionine induced apoptosis. Selenomethionine administration to thecancer cell lines increased the number of cells in metaphase. This cellcycle effect appeared to be reversed with the co-administration ofselenomethionine and spermine. These data suggested that at least part ofthe anti- carcinogenic effects of selenium supplementation might be due toa depletion in polyamine levels. This depletion of polyamines leads to aninduction in apoptosis and perturbations in the cell cycle.