Pharmaceutical Research

, Volume 27, Issue 6, pp 1115–1127

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

  • Vinita Singh-Gupta
  • Hao Zhang
  • Christopher K. Yunker
  • Zahra Ahmad
  • Danielle Zwier
  • Fazlul H. Sarkar
  • Gilda G. Hillman
Research Paper

DOI: 10.1007/s11095-010-0107-9

Cite this article as:
Singh-Gupta, V., Zhang, H., Yunker, C.K. et al. Pharm Res (2010) 27: 1115. doi:10.1007/s11095-010-0107-9

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.

KEY WORDS

androgen receptor prostate cancer radiation soy isoflavones 

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

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Vinita Singh-Gupta
    • 1
  • Hao Zhang
    • 1
  • Christopher K. Yunker
    • 1
  • Zahra Ahmad
    • 1
  • Danielle Zwier
    • 1
  • Fazlul H. Sarkar
    • 2
  • Gilda G. Hillman
    • 1
  1. 1.Department of Radiation OncologyWayne State University School of MedicineDetroitUSA
  2. 2.Department of Pathology, Barbara Ann Karmanos Cancer InstituteWayne State University School of MedicineDetroitUSA

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