Mechanisms of the growth inhibitory effects of the isoflavonoid biochanin A on LNCaP cells and xenografts
| Autor: | Lori Rice, Henry V. Baker, Jaime Furman, Von G. Samedi, Anne Stenstrom, Theresa Medrano, Carol A. Sweeney, Kathleen T. Shiverick |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Programmed cell death Cell cycle checkpoint DNA Complementary Urology Transplantation Heterologous Mice Nude Cell Cycle Proteins Biology Biochanin A Flow cytometry chemistry.chemical_compound Mice Internal medicine LNCaP medicine Tumor Cells Cultured Animals Anticarcinogenic Agents Humans Oligonucleotide Array Sequence Analysis medicine.diagnostic_test Cell growth Prostatic Neoplasms Molecular biology Genistein Endocrinology Oncology chemistry Apoptosis DNA fragmentation Cell Division Neoplasm Transplantation |
| Zdroj: | The Prostate. 52(3) |
| ISSN: | 0270-4137 |
| Popis: | 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 [3H]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 G0/G1 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. |
| Databáze: | OpenAIRE |
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