Premium
Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts *
Author(s) -
Rice Lori,
Samedi Von G.,
Medrano Theresa A.,
Sweeney Carol A.,
Baker Henry V.,
Stenstrom Anne,
Furman Jaime,
Shiverick Kathleen T.
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10100
Subject(s) - biochanin a , lncap , cell cycle , cancer research , dna fragmentation , biology , apoptosis , cell growth , prostate cancer , microbiology and biotechnology , programmed cell death , endocrinology , cancer , daidzein , genistein , biochemistry , genetics
BACKGROUND Isoflavones inhibit the growth of some types of tumor cells, including prostate adenocarcinoma. This study used LNCaP cells and xenografts to investigate the mechanisms of the antiproliferative effects of biochanin A, a major isoflavone present in red clover but not soy‐derived products. METHODS LNCaP cells were exposed to varying doses of biochanin A to evaluate viability, DNA synthesis, and DNA fragmentation (TUNEL) analysis. Regulation of gene expression was determined by using Western immunoblotting and cDNA microarrays. Anti‐tumorigenic effects were evaluated by using athymic mice with LNCaP flank tumors. RESULTS Biochanin A induced a dose‐dependent inhibition of proliferation and [ 3 H]thymidine incorporation that correlated with increased DNA fragmentation, indicative of apoptosis. Western blot analyses of cell cycle regulatory proteins revealed that biochanin A significantly decreased expression of cyclin B and p21, whereas flow cytometry showed that cells were accumulating in the G 0 /G 1 phase. cDNA microarray analyses identified 29 down‐regulated genes with six reduced below assay detection limits. Eleven genes were up‐regulated, including 9 that were undetectable in controls. In mice with LNCaP xenografts, biochanin A significantly reduced tumor size and incidence. CONCLUSION These results indicate that biochanin A inhibits prostate cancer cell growth through induction of cell cycle arrest and apoptosis. Biochanin A‐regulated genes suggest multiple pathways of action. Biochanin A inhibits the incidence and growth of LNCaP xenograft tumors in athymic mice. Prostate 52:201–212, 2002. © 2002 Wiley‐Liss, Inc.