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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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ABSTRACT

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.

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Abbreviations

Ab:

Antibody

APE/Ref-1:

Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1

AR:

Androgen Receptor

AR−:

Androgen Receptor negative

AR+:

Androgen Receptor positive

CM:

Culture medium

EMSA:

Electrophoretic mobility shift assay

FBS:

Fetal bovine serum

HIF-1α:

Hypoxia Inducible factor 1 alpha

NF-κB:

Nuclear Factor kappa B

PARP:

poly-APD-ribose-polymerases

PBS:

Phosphate buffered saline

PCa:

Prostate Cancer

RCC:

Renal cell carcinoma

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ACKNOWLEDGEMENTS

This study was supported by the Fund for Cancer Research (grant to G.G.H.), American Cancer Society (grant ROG-06-097-01 to G.G.H.) and the American Institute for Cancer Research (grant 03B108 to G.G.H.). We thank Amit Patel for excellent technical assistance.

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Authors and Affiliations

  1. Department of Radiation Oncology, Wayne State University School of Medicine, 515 Hudson-Webber Cancer Research Center, 4100 John R. Road, Detroit, Michigan, 48201, USA

    Vinita Singh-Gupta, Hao Zhang, Christopher K. Yunker, Zahra Ahmad, Danielle Zwier & Gilda G. Hillman

  2. Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA

    Fazlul H. Sarkar

Authors
  1. Vinita Singh-Gupta
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  2. Hao Zhang
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  3. Christopher K. Yunker
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  4. Zahra Ahmad
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  5. Danielle Zwier
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  6. Fazlul H. Sarkar
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  7. Gilda G. Hillman
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Correspondence to Gilda G. Hillman.

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Singh-Gupta, V., Zhang, H., Yunker, C.K. et al. Daidzein Effect on Hormone Refractory Prostate Cancer In Vitro and In Vivo Compared to Genistein and Soy Extract: Potentiation of Radiotherapy. Pharm Res 27, 1115–1127 (2010). https://doi.org/10.1007/s11095-010-0107-9

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  • DOI: https://doi.org/10.1007/s11095-010-0107-9

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