Abstract
Introduction
Phytoestrogen apigenin, a member of flavonoids, has been described for its ability
to induce growth arrest in carcinomas of colon, breast and prostate. In order to identify
its influence on the prostatic stroma, which plays a crucial role in the pathogenesis
of benign prostatic hyperplasia (BPH), we investigated the effect of apigenin on cell
proliferation and cell-cycle progression.
Methods
Prostatic stromal cells were isolated from nonmalignant tissue specimens obtained
from patients undergoing radical prostatectomy. After incubation with increasing concentrations
of apigenin for 24, 48 and 72 h the cell proliferation was determined by MTT assay. Cell-cycle regulation was examined
by FACS analysis and the expression level of proteins involved in the G1/S transition
was determined by immunoblot analysis.
Results
Apigenin treatment resulted in a significant inhibition of proliferation starting
at a concentration of 30 μM of the flavonoid. FACS analysis showed cell-cycle arrest at a G1/S transition point.
Furthermore, apigenin modified the expression levels of cell-cycle regulatory proteins
leading to a dose-dependent decrease of cyclin D1 and an increase of p21/WAF1 expression,
as determined by immunoblot analysis. As apigenin lead to a decrease of the phosphorylation
status of ERK1 and 2, we postulated that the mechanism of apigenin action is mediated
through mitogen activated kinases (MAPK)-pathway.
Conclusion
Taken together, in response to apigenin treatment prostatic stromal cells showed a
dose-dependent inhibition of cell proliferation, which may be due to a cell-cycle
growth arrest and seems to occur via MAPK-pathway. These results suggest possible
beneficial effects of apigenin in the prevention and/or treatment of benign prostatic
hyperplasia.
Keywords
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References
- Benign prostatic hyperplasia.Lancet. 2003; 361: 1359-1367
- Hormone-induced morphogenesis and growth: role of mesenchymal–epithelial interactions.Recent Prog Horm Res. 1983; 39: 559-598
- Changes in the prevalence of benign prostatic hyperplasia in China.Chin Med J (Engl). 1997; 110: 163-166
- Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet.Am J Clin Nutr. 1991; 54: 1093-1100
- Plasma concentrations of phyto-oestrogens in Japanese men.Lancet. 1993; 342: 1209-1210
- Phytoestrogens: potential endocrine disruptors in males.Toxicol Ind Health. 1998; 14: 223-237
- Inhibition of 5 alpha-reductase in genital skin fibroblasts and prostate tissue by dietary lignans and isoflavonoids.J Endocrinol. 1995; 147: 295-302
- Phytoestrogens and inhibition of angiogenesis.Baillieres Clin Endocrinol Metab. 1998; 12: 649-666
- Mechanisms of action of the soy isoflavone genistein: emerging role for its effects via transforming growth factor beta signaling pathways.Am J Clin Nutr. 1998; 68: 1418S-1425S
- Soy for breast cancer survivors: a critical review of the literature.J Nutr. 2001; 131: 3095S-3108S
- Comparative study of concentration of isoflavones and lignans in plasma and prostatic tissues of normal control and benign prostatic hyperplasia.Yonsei Med J. 2002; 43: 236-241
- Plant-derived phenolic antioxidants.Curr Opin Lipidol. 2000; 11: 43-47
- The effect of cytokine mediators on prostaglandin inhibition by human decidual cells.Am J Obstet Gynecol. 1998; 179: 146-149
- Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines.Mol Carcinog. 2000; 28: 102-110
- Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.Int J Cancer. 2000; 87: 595-600
- Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice.Cancer Res. 1990; 50: 499-502
- Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells.Biochem Biophys Res Commun. 2001; 287: 914-920
- Screening for prostate cancer: updated experience from the Tyrol study.Curr Urol Rep. 2004; 5: 220-225
- Modulation of the differentiation status of cultured prostatic smooth muscle cells by an alpha1-adrenergic receptor antagonist.Prostate. 1999; 39: 226-233
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem. 1976; 72: 248-254
- Role of androgens in prostatic cancer.Vitam Horm. 1994; 49: 433-502
- Estrogen receptor expression in developing epididymis, efferent ductules, and other male reproductive organs.Endocrinology. 1991; 128: 2874-2879
- Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells.Oncogene. 2002; 21: 3727-3738
- Androgen receptor regulation by physiological concentrations of the isoflavonoid genistein in androgen-dependent LNCaP cells is mediated by estrogen receptor beta.Eur Urol. 2004; 45 ([discussion 251]): 245-251
- Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.Endocrinology. 1998; 139: 4252-4263
- Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents.Biochem Pharmacol. 2000; 60: 1051-1059
Article info
Publication history
Published online: July 20, 2006
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
