Selenocystine induces S-phase arrest and apoptosis in human breast adenocarcinoma MCF-7 cells by modulating ERK and Akt phosphorylation.
Selenocystine (SeC) is a nutritionally available selenoamino acid with selective anticancer effects on a number of human cancer cell lines. The present study shows that SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt. Inhibitors of ERK (U0126) and Akt (LY294002), but not JNK (SP600125) and p38 MAPK (SB203580), suppressed SeC-induced S-phase arrest and apoptosis in MCF-7 cells. The findings establish a mechanistic link between the PI3K/Akt pathway, MAPK pathway, and SeC-induced cell cycle arrest and apoptosis in MCF-7 cells.
Chen
Tianfeng
T
Department of Biology, State Key Laboratory China for Agrobiotechnology and Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Hong Kong, China.
Wong
Yum-Shing
YS
D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects*
D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; C009226:selenocystine; D003553:Cystine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases