Differences between human breast cell lines in susceptibility towards growth inhibition by genistein.
Genistein is thought to contribute to the putative breast cancer preventive activity of soya. The mechanisms by which it arrests the growth of breast cells are incompletely understood. In order to explore generic features of the modulation of human breast cell growth by genistein, its effects on cell lines MCF-7, ZR-75.1, T47-D, MDA-MB 468, MDA-MB 231 and HBL 100 were compared. Genistein at 1 microM stimulated growth only in MCF-7 cells. At 10 microM it arrested the growth of all 6 cell types, however that of T47-D and HBL 100 cells only in medium with reduced (2%) fetal calf serum. Genistein induced apoptosis in only MDA-MB 468 cells. It arrested cells in the G2 stage of the cell cycle in all cell lines except ZR-75.1. Cells differed in their susceptibility towards inhibition by genistein of phorbol ester-induced proto-oncogene c-fos levels, transcription factor activator protein-1 (AP-1) activity and extracellular signal-regulated kinase (ERK) activity. Genistein augmented anisomycin-induced levels of proto-oncogene c-jun in ZR 75.1 and MCF-7 cells. The results suggest that induction of apoptosis, G2 cell cycle arrest and inhibition of c-fos expression, AP-1 transactivation and ERK phosphorylation may contribute to the growth-inhibitory effect of genistein in some breast cell types, but none of these effects of genistein constitutes a generic mode of growth-arresting action.
Dampier
K
K
MRC Toxicology Unit, University of Leicester, PO Box 138, Leicester LE1 9HN, UK.
Hudson
E A
EA
Howells
L M
LM
Manson
M M
MM
Walker
R A
RA
Gescher
A
A
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle; D018890:Chemoprevention; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000494:pharmacology; D015398:Signal Transduction; D013025:Glycine max; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D019833:Genistein; D020928:Mitogen-Activated Protein Kinases