Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line.
Lung cancer is the leading cause of cancer-related death in the world, with increasing incidence in many developed countries. Epidemiological data suggest that consumption of soy products (the isoflavone genistein) may be associated with a decreased risk of breast and prostate cancer; however, such studies are not available for lung cancer. We investigated cell growth inhibition, modulation in gene expression, and induction of apoptosis by genistein in H460 non-small lung cancer cells. Genistein inhibited H460 cell growth in a dose-dependent manner. Flow-cytometric analysis showed that 30 microM genistein arrested cell cycle progression at the G2-M phase. 4,6-Diamidino-2-phenylindole staining, flow-cytometric analysis, and DNA laddering were used to investigate apoptotic cell death, and the results show that 30 microM genistein can cause typical DNA laddering, a hallmark for apoptosis. In addition, flow cytometry and 4,6-diamidino-2-phenylindole staining showed induction of apoptosis by genistein. Our investigation also demonstrated the modulation of p21WAF1 by Western blot analysis of cell lysates obtained from cultured cells treated with 30 and 50 microM genistein for 24, 48, and 72 hours. Simultaneously, immunocytochemical staining was conducted for the expression of p21WAF1 protein. Our results showed that genistein can upregulate p21WAF1 expression in genistein-treated cells. From these results, we conclude that genistein may act as an anticancer agent, and further studies may prove its efficacy in non-small lung cancer cells. Thus the biological effects of genistein may, indeed, be due to the modulation of cell growth, cell death, and cell cycle regulatory molecules.
Lian
F
F
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Bhuiyan
M
M
Li
Y W
YW
Wall
N
N
Kraut
M
M
Sarkar
F H
FH
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019833:Genistein