Molecular mechanisms associated with Se-allylselenocysteine regulation of cell proliferation and apoptosis.
Se-allylselenocysteine (ASC) has been shown to inhibit mammary carcinogenesis in vivo and cell growth in vitro. However, little is known about the molecular events that account for these effects. The goal of the present study was to use a mouse hyperplastic mammary epithelial cell line, TM12, to investigate the underlying mechanism(s) associated with ASC regulation of cell proliferation and apoptosis. Cells were treated with 50 microM ASC and assessed after 3, 6 and 12 h of exposure. A significant inhibition of cell proliferation, as measured by BrdU incorporation into DNA, was observed within 3 h of ASC treatment. This inhibitory effect was slightly magnified at the later time points. The induction of apoptosis was also rapid, and progressed from a 1.3-fold increase at 3 h to a 4.4-fold increase at 12 h. Consistent with these cellular events, the levels of phosphorylated Rb protein were greatly reduced at all times points. The other accompanying changes included increases in P53, P21 and P27. Collectively, the results demonstrate for the first time that ASC is able to cause an immediate response in the expression of cell cycle regulatory proteins that favor an arrest in proliferation and an augmentation in apoptosis.
Jiang
W
W
Center for Nutrition in the Prevention of Disease, AMC Cancer Research Center, Lakewood, CO 80214, USA.
Zhu
Z
Z
Ganther
H E
HE
Ip
C
C
Thompson
H J
HJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006131:Growth Inhibitors / Q000494:pharmacology*; D006965:Hyperplasia / Q000473:pathology; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D017279:Selenocysteine / Q000031:analogs & derivatives / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D006131:Growth Inhibitors; D016566:Organoselenium Compounds; D016160:Retinoblastoma Protein; C415427:Se-allylselenocysteine; D017279:Selenocysteine