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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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.
- Hillman GG, Forman JD, Kucuk O, Yudelev M, Maughan RL, Rubio J et al. Genistein potentiates the radiation effect on prostate carcinoma cells. Clin Cancer Res. 2001;7:382–90.
- Raffoul JJ, Wang Y, Kucuk O, Forman JD, Sarkar FH, Hillman GG. Genistein inhibits radiation-induced activation of NF-kappaB in prostate cancer cells promoting apoptosis and G2/M cell cycle arrest. BMC Cancer. 2006;6:107. CrossRef
- Hillman GG, Wang Y, Kucuk O, Che M, Doerge DR, Yudelev M et al. Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model. Mol Cancer Ther. 2004;3:1271–9.
- Raffoul JJ, Banerjee S, Singh-Gupta V, Knoll ZE, Fite A, Zhang H et al. Down-regulation of apurinic/apyrimidinic endonuclease 1/redox factor-1 expression by soy isoflavones enhances prostate cancer radiotherapy in vitro and in vivo. Cancer Res. 2007;67:2141–9. CrossRef
- Raffoul JJ, Banerjee S, Che M, Knoll ZE, Doerge DR, Abrams J et al. Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model. Int J Cancer. 2007;120:2491–8. CrossRef
- Singh-Gupta V, Zhang H, Banerjee S, Kong D, Raffoul JJ, Sarkar FH et al. Radiation-induced HIF-1alpha cell survival pathway is inhibited by soy isoflavones in prostate cancer cells. Int J Cancer. 2009;124:1675–84. CrossRef
- Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer Metastasis Rev. 2002;21:265–80. CrossRef
- Hebert JR, Hurley TG, Olendzki BC, Teas J, Ma Y, Hampl JS. Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. J Natl Cancer Inst. 1998;90:1637–47. CrossRef
- Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;349:366–81. CrossRef
- Walsh PC, DeWeese TL, Eisenberger MA. Clinical practice. Localized prostate cancer. N Engl J Med. 2007;357:2696–705. CrossRef
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49. CrossRef
- Zietman AL, DeSilvio ML, Slater JD, Rossi Jr CJ, Miller DW, Adams JA et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294:1233–9. CrossRef
- Swanson GP, Hussey MA, Tangen CM, Chin J, Messing E, Canby-Hagino E et al. Predominant treatment failure in postprostatectomy patients is local: analysis of patterns of treatment failure in SWOG 8794. J Clin Oncol. 2007;25:2225–9. CrossRef
- Morgan PB, Hanlon AL, Horwitz EM, Buyyounouski MK, Uzzo RG, Pollack A. Radiation dose and late failures in prostate cancer. Int J Radiat Oncol Biol Phys. 2007;67:1074–81.
- Sarkar FH, Li Y, Wang Z, Kong D. Cellular signaling perturbation by natural products. Cell Signal. 2009;21:1541–7. CrossRef
- Sarkar FH, Li Y. Using chemopreventive agents to enhance the efficacy of cancer therapy. Cancer Res. 2006;66:3347–50. CrossRef
- Lo FH, Mak NK, Leung KN. Studies on the anti-tumor activities of the soy isoflavone daidzein on murine neuroblastoma cells. Biomed Pharmacother. 2007;61:591–5. CrossRef
- Choi EJ, Kim GH. Daidzein causes cell cycle arrest at the G1 and G2/M phases in human breast cancer MCF-7 and MDA-MB-453 cells. Phytomedicine. 2008;15:683–90. CrossRef
- Davis JN, Singh B, Bhuiyan M, Sarkar FH. Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells. Nutr Cancer. 1998;32:123–31. CrossRef
- Davis JN, Kucuk O, Sarkar FH. Genistein inhibits NF-kappa B activation in prostate cancer cells. Nutr Cancer. 1999;35:167–74. CrossRef
- Wang Y, Raffoul JJ, Che M, Doerge DR, Joiner MC, Kucuk O et al. Prostate cancer treatment is enhanced by genistein in vitro and in vivo in a syngeneic orthotopic tumor model. Radiat Res. 2006;166:73–80. CrossRef
- Hillman GG, Wang Y, Che M, Raffoul JJ, Yudelev M, Kucuk O et al. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model. BMC Cancer. 2007;7:4. CrossRef
- Hussain M, Banerjee M, Sarkar FH, Djuric Z, Pollak MN, Doerge D et al. Soy isoflavones in the treatment of prostate cancer. Nutr Cancer. 2003;47:111–7. CrossRef
- Raffoul JJ, Sarkar FH, Hillman GG. Radiosensitization of prostate cancer by soy isoflavones. Curr Cancer Drug Targets. 2007;7:759–65. CrossRef
- Evans AR, Limp-Foster M, Kelley MR. Going APE over ref-1. Mutat Res. 2000;461:83–108.
- Thalmann GN, Anezinis PE, Chang SM, Zhau HE, Kim EE, Hopwood VL et al. Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res. 1994;54:2577–81.
- Bhuiyan MM, Li Y, Banerjee S, Ahmed F, Wang Z, Ali S et al. Down-regulation of androgen receptor by 3, 3′-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4–2B prostate cancer cells. Cancer Res. 2006;66:10064–72. CrossRef
- Mentor-Marcel R, Lamartiniere CA, Eltoum IE, Greenberg NM, Elgavish A. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP). Cancer Res. 2001;61:6777–82.
- Aronson WJ, Tymchuk CN, Elashoff RM, McBride WH, McLean C, Wang H et al. Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones. Nutr Cancer. 1999;35:130–6. CrossRef
- Lamartiniere CA, Murrill WB, Manzolillo PA, Zhang JX, Barnes S, Zhang X et al. Genistein alters the ontogeny of mammary gland development and protects against chemically-induced mammary cancer in rats. Proc Soc Exp Biol Med. 1998;217:358–64.
- Lamartiniere CA, Cotroneo MS, Fritz WA, Wang J, Mentor-Marcel R, Elgavish A. Genistein chemoprevention: timing and mechanisms of action in murine mammary and prostate. J Nutr. 2002;132:552S–8.
- Zhou JR, Gugger ET, Tanaka T, Guo Y, Blackburn GL, Clinton SK. Soybean phytochemicals inhibit the growth of transplantable human prostate carcinoma and tumor angiogenesis in mice. J Nutr. 1999;129:1628–35.
- Zhou JR, Yu L, Zhong Y, Nassr RL, Franke AA, Gaston SM et al. Inhibition of orthotopic growth and metastasis of androgen-sensitive human prostate tumors in mice by bioactive soybean components. Prostate. 2002;53:143–53. CrossRef
- Rao CV, Rivenson A, Simi B, Zang E, Hamid R, Kelloff GJ et al. Enhancement of experimental colon carcinogenesis by dietary 6-phenylhexyl isothiocyanate. Cancer Res. 1995;55:4311–8.
- Cohen LA, Zhao Z, Pittman B, Scimeca J. Effect of soy protein isolate and conjugated linoleic acid on the growth of Dunning R-3327-AT-1 rat prostate tumors. Prostate. 2003;54:169–80. CrossRef
- Wietrzyk J, Mazurkiewicz M, Madej J, Dzimira S, Grynkiewicz G, Radzikowski C et al. Genistein alone or combined with cyclophosphamide may stimulate 16/C transplantable mouse mammary cancer growth. Med Sci Monit. 2004;10:BR414–9.
- Tepper CG, Vinall RL, Wee CB, Xue L, Shi XB, Burich R et al. GCP-mediated growth inhibition and apoptosis of prostate cancer cells via androgen receptor-dependent and -independent mechanisms. Prostate. 2007;67:521–35. CrossRef
- Wouters A, Pauwels B, Lardon F, Vermorken JB. Review: implications of in vitro research on the effect of radiotherapy and chemotherapy under hypoxic conditions. Oncologist. 2007;12:690–712. CrossRef
- Fishel ML, Kelley MR. The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. Mol Aspects Med. 2007;28:375–95. CrossRef
- Harada H, Kizaka-Kondoh S, Li G, Itasaka S, Shibuya K, Inoue M et al. Significance of HIF-1-active cells in angiogenesis and radioresistance. Oncogene. 2007;26:7508–16. CrossRef
- Daidzein Effect on Hormone Refractory Prostate Cancer In Vitro and In Vivo Compared to Genistein and Soy Extract: Potentiation of Radiotherapy
Volume 27, Issue 6 , pp 1115-1127
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- androgen receptor
- prostate cancer
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- Author 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
- 2. Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, 48201, USA