Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells.
The efficacy of dietary selenium supplementation is currently being evaluated in intervention trials. However, the biological mechanisms underlying the cancer chemopreventive effects of selenium supplementation have yet to be elucidated. Selenium metabolism and polyamine biosynthesis are linked in their common requirement for S-adenosylmethionine. Selenomethionine was the predominant form of selenium in the dietary supplement, therefore we evaluated the anti-tumorigenic effects of selenomethionine. 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 was decreased at doses that inhibited 50% of normal growth. Selenomethionine treatment induced apoptosis in both cancer cell lines. Exogenous spermine administration, which replenishes intracellular polyamine levels, prevented selenomethionine induced apoptosis. Selenomethionine administration to the cancer cell lines increased the number of cells in metaphase. This cell cycle effect appeared to be reversed with the co-administration of selenomethionine and spermine. These data suggested 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 perturbations in the cell cycle.
Redman
C
C
Pharmacology/Toxicology Department, The Arizona Cancer Center, The University of Arizona, Tucson 85724, USA.
Xu
M J
MJ
Peng
Y M
YM
Scott
J A
JA
Payne
C
C
Clark
L C
LC
Nelson
M A
MA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015317:Biogenic Polyamines / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008935:Mitoguazone / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D012645:Selenomethionine / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D013096:Spermine; D012645:Selenomethionine; D008935:Mitoguazone