In vitro effects of Se-allylselenocysteine and Se-propylselenocysteine on cell growth, DNA integrity, and apoptosis.
Two previously unevaluated selenium compounds, Se-allylselenocysteine (ASC) and Se-propylselenocysteine (PSC), have been shown recently to be active in the chemoprevention of experimentally induced mammary carcinogenesis. Other than their potential as chemopreventive agents, little is known about the pharmacological properties of these compounds. In this article, we report on the in vitro effects of ASC and PSC on cell growth inhibition, apoptosis, and the induction of DNA damage. The effects of ASC and PSC were examined in two mouse mammary epithelial cell lines derived from mammary hyperplasias. These cell lines, designated TM2H and TM12, have mutant or wild-type p53, respectively. It was observed that ASC but not PSC reduced, in a concentration- and time-dependent manner, the number of adherent cells in culture, and this suppressive effect was more prominent in TM12 than in TM2H cells. ASC was also found to induce alkaline-labile DNA damage and the oxidation of pyrimidines, and it also increased the rate of apoptosis. These changes were not seen by exposure to PSC or the sulfur analog of ASC. However, additional data obtained from the intact rat mammary gland suggest that the loss of DNA integrity induced by ASC might not be manifest in vivo at doses of ASC that inhibit carcinogenesis.
Zhu
Z
Z
Center for Nutrition in the Prevention of Disease, AMC Cancer Research Center, Lakewood, CO 80214, USA.
Jiang
W
W
Ganther
H E
HE
Ip
C
C
Thompson
H J
HJ
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D008190:Lyases / Q000378:metabolism; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D017279:Selenocysteine / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016566:Organoselenium Compounds; C415427:Se-allylselenocysteine; C415428:Se-propylselenocysteine; D017279:Selenocysteine; D004247:DNA; D008190:Lyases; C034278:selenocysteine lyase