Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells

• Published in: European journal of cancer (1990) Vol. 34; no. 12; pp. 1927 - 1934
• Main Authors: Constantinou, A.I, Kamath, N, Murley, J.S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.1998; Elsevier
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; apoptosis, genistein, p53, bcl-2, topoisomerase; Biological and medical sciences; Blotting, Northern; Blotting, Western; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Chemotherapy; Down-Regulation; Female; Genistein - pharmacology; Genistein - therapeutic use; Humans; Medical sciences; Pharmacology. Drug treatments; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - metabolism; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - metabolism; Up-Regulation; apoptosis, genistein, p53, bcl-2, topoisomerase; Adenocarcinoma; Antineoplastic agent; Human; Cell culture; Malignant tumor; Soybean; In vitro; Isoflavone derivatives; Northern blotting; Mammary gland diseases; C-Onc gene; Cell cycle; Established cell line; Immunoblotting assay; Mammary gland; Molecular biology; Mechanism of action; Protooncogene; Apoptosis
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(98)00198-1

The aim of this study was to identify the molecular mechanism of action of the isoflavone, genistein. Genistein at 0.15 mM caused MCF-7 apoptotic cell death, which was accompanied by cell cycle delay in the G2/M phase. Twenty-four hours post-treatment, 47.3% of the MCF-7 cells accumulated at G2/M, compared with 19.9% in the untreated controls. At 0.15 mM, genistein caused an increase in the steady-state levels of the wild-type tumour suppressor p53, which was attributed to stabilising the tumour suppressor protein, since p53 mRNA levels did not increase. Prior to the upregulation of p53, which became evident within 6 h of genistein treatment, there was increased bcl-2 phosphorylation at 30 min post-treatment. Although early changes (30–120 min) in the phosphotyrosine peptide patterns were not detected, after 24 h, genistein inhibited phosphorylation of several peptides. These results suggest that genistein’s dual roles of protein tyrosine kinase inhibitor and topoisomerase II inhibitor are essential for the initiation of apoptosis.