Doenjang hexane fraction-induced G1 arrest is associated with the inhibition of pRB phosphorylation and induction of Cdk inhibitor p21 in human breast carcinoma MCF-7 cells.
Doenjang (fermented soy paste) is a Korean traditional fermented food. In previous studies, we demonstrated that Doenjang extracts exhibited anti-mutagenic and anti-carcinogenic activities. Here we investigated the effects of Doenjang hexane fraction (DHF) on cell cycle progression in the human breast carcinoma MCF-7 cells. Treatment of DHF to MCF-7 cells induced a G1 phase arrest of the cell cycle, which correlated with the accumulation of the hypophosphorylated form of the retinoblastoma protein (pRB) and enhanced association of pRB with the transcription factor E2F-1. After DHF treatment, the expression of D-type cyclins was decreased in a time-dependent manner, but DHF did not affect the levels of cyclin-dependent kinases (Cdks), cyclin E and cyclin A protein. However, the activity of Cdk2 and cyclin E-associated kinase was decreased in a time-dependent manner. The tumor suppressor p53 and Cdk inhibitor p21, a known downstream effector of the p53, and association of p21 with Cdk2 were markedly induced in DHF-treated cells. Taken together, the present results indicate that treatment of MCF-7 cells with DHF induces a significant inhibition of pRB phosphorylation and increase of Cdk inhibitor p21 that appear to be responsible for the observed G1 arrest.
Choi
Y H
YH
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University, Pusan 614-054, Korea. choiyh@hyomin.dongeui.ac.kr
Choi
B T
BT
Lee
W H
WH
Rhee
S H
SH
Park
K Y
KY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects*; D056741:Cyclin D; D019927:Cyclin E; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis* / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004790:Enzyme Induction; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D030262:Soybean Proteins / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D056741:Cyclin D; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D030262:Soybean Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases