Daidzein Effect on Hormone Refractory Prostate Cancer In Vitro and In Vivo Compared to Genistein and Soy Extract: Potentiation of Radiotherapy

• Published in: Pharmaceutical research Vol. 27; no. 6; pp. 1115 - 1127
• Main Authors: Singh-Gupta, Vinita, Zhang, Hao, Yunker, Christopher K, Ahmad, Zahra, Zwier, Danielle, Sarkar, Fazlul H, Hillman, Gilda G
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.06.2010; Springer US; Springer Nature B.V
• Subjects: androgen receptor; Androgens - metabolism; Animals; Antineoplastic Agents - therapeutic use; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; DNA - metabolism; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Genistein - adverse effects; Glycine max - chemistry; Hormones; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Isoflavones - therapeutic use; Lymph Nodes - drug effects; Lymph Nodes - pathology; Lymph Nodes - radiation effects; Male; Medical Law; Mice; NF-kappa B - metabolism; Pharmacology/Toxicology; Pharmacy; Plant Extracts - therapeutic use; Prostate cancer; prostatic neoplasms; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Prostatic Neoplasms - secondary; radiation; Radiation therapy; Radiation-Sensitizing Agents - adverse effects; Research Paper; Rodents; soy isoflavones; Soy products; prostate cancer; androgen receptor; radiation; soy isoflavones
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-010-0107-9

Purpose Genistein, the major bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer (PCa) both in vitro and in vivo. However, pure genistein promoted increased metastasis to lymph nodes. A mixture of soy isoflavones (genistein, daidzein, glycitein) did not cause increased metastasis, but potentiated radiotherapy. We tested whether daidzein could negate genistein-induced metastasis. Methods Mice bearing PC-3 prostate tumors were treated with daidzein, genistein or both, and with tumor irradiation. Primary tumors and metastases were evaluated. The effects of each isoflavone and soy were compared in vitro using PC-3 (AR−) and C4-2B (AR+) androgen-independent PCa cell lines. Results Daidzein did not increase metastasis to lymph nodes and acted as a radiosensitizer for prostate tumors. Daidzein inhibited cell growth and enhanced radiation in vitro but at doses higher than genistein or soy. Daidzein caused milder effects on inhibition of expression and/or activities of APE1/Ref-1, HIF-1α and NF-κB in PC-3 and C4-2B cells. Conclusions Daidzein could be the component of soy that protects against genistein-induced metastasis. Daidzein inhibited cell growth and synergized with radiation, affecting APE1/Ref-1, NF-κB and HIF-1α, but at lower levels than genistein and soy, in AR+ and AR- PCa cells, suggesting it is an AR-independent mechanism.