Cellular and metabolic effects of triphenylselenonium chloride in a mammary cell culture model.
Triphenylselenonium chloride, a novel synthetic organic selenium compound in which selenium is bonded to three unsubstituted benzene rings, possesses significant chemopreventive activity against chemically-induced mammary carcinogenesis. The effects of triphenylselenonium chloride on a mammary tumor cell line (MOD) were compared to selenite, a reference compound in selenium chemoprevention research. It was observed that triphenylselenonium chloride treatment exerted a cytostatic effect in the absence of membrane damage or DNA strand breaks. The observed cytostasis was associated with a selenium concentration-dependent inhibition of cell proliferation, measured by [3H]thymidine incorporation into DNA, and delayed cell cycle progression. In contrast, selenite treatment rapidly induced DNA damage and cell death. These marked differences were observed across the same levels of cellular selenium. In addition, triphenylselenonium chloride treatment increased glucose consumption and lactate production, indicating an effect of the compound on cellular energy metabolism. Collectively these observations demonstrate that the toxic activities associated with selenite treatment do not occur when cells are treated with triphenylselenonium chloride. This compound represents a new type of selenium compound that exerts significant cellular effects through mechanisms distinct from those induced by selenite.
Lu
J
J
Division of Laboratory Research, AMC Cancer Research Center, Denver, CO 80214.
Jiang
C
C
Kaeck
M
M
Ganther
H
H
Ip
C
C
Thompson
H
H
D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D004247:DNA / Q000187:drug effects; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018036:Selenium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000633:toxicity; D014407:Tumor Cells, Cultured
D016566:Organoselenium Compounds; D018036:Selenium Compounds; C092819:triphenylselenonium chloride; D004247:DNA; D018038:Sodium Selenite