Daidzein Effect on Hormone Refractory Prostate Cancer In Vitro and In Vivo Compared to Genistein and Soy Extract: Potentiation of Radiotherapy
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- Singh-Gupta, V., Zhang, H., Yunker, C.K. et al. Pharm Res (2010) 27: 1115. doi:10.1007/s11095-010-0107-9
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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.
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.
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.
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.
KEY WORDSandrogen receptor prostate cancer radiation soy isoflavones
Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1
Androgen Receptor negative
Androgen Receptor positive
Electrophoretic mobility shift assay
Fetal bovine serum
Hypoxia Inducible factor 1 alpha
Nuclear Factor kappa B
Phosphate buffered saline
Renal cell carcinoma