Effects of Flavonoids Genistein and Biochanin A on Gene Expression and Their Metabolism in Human Mammary Cells

Abstract

Genistein (GEN) and biochanin A (BCA), dietary isoflavones, possess breast cancer–preventive properties. Our objective was to examine the effect of physiologically relevant concentrations of BCA and GEN on gene expression in normal (HMEC), immortalized but nontumorigenic (MCF12A), and tumorigenic (MCF7) mammary cells and to determine whether the differences in gene expression are related to differences in metabolism in the three types of mammary cells. Using cDNA arrays, we compared the gene expression after a 48-h incubation with 1 μ M BCA, GEN, or vehicle. Treatment with GEN or BCA produced the greatest number of significant changes in HMEC compared with MCF12A or MCF7 cells. Unlike GEN, effects of BCA on gene expression were mostly beneficial, involving induction of tumor suppressor genes. Different extents of metabolism were observed in the three mammary cell types; however, GEN concentrations were very low following either GEN or BCA administration in all of the three cell types. Because there were only very low concentrations of GEN, compared with BCA concentrations, in HMEC and MCF12A cells treated with BCA and different gene expression changes were found after BCA and GEN treatment, these findings suggest that BCA has distinct effects compared with GEN. The results suggest that BCA may represent a better breast cancer–preventive agent than GEN.

Acknowledgments and Notes

We thank Dr. Kazuko Sagawa of Pfizer for performing the LC/MS/MS assay. This work was supported by grants from the Susan G. Komen Foundation, Cancer Research and Prevention Foundation, and Kapoor Charitable Foundation, University at Buffalo.

Address correspondence to M. E. Morris, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Amherst, NY, 14260. Phone: [phone] (X230). FAX: [phone]. E-mail: [email protected]