Isoflavones
Isoflavones da soja no tratamento do câncer de próstata
Soy Isoflavones in the Treatment of Prostate Cancer.
Maha Hussain1, Fazlul H. Sarkar2, Zora Djuric1, Michael N. Pollak3, Mousumi Banerjee4, Daniel Doerge5, Joseph Fontana1,6, Sreenivasa Chinni2, Joanne Davis2, Jeffrey Forman7, David P. Wood8, and Omer Kucuk1,
1Division of Hematology and Oncology,
2Department of Pathology, 7Department of Radiation Oncology, 8Department of Urology, and 4Center for Healthcare Effectiveness Research, Wayne State University and the Barbara Ann Karmanos Cancer Institute, 3990 John R Street, Detroit, MI 48201, USA; 6VA Medical Center, Detroit, MI; 3Department of Medicine, McGill University and Jewish General Hospital, Montreal, Quebec, Canada; 5Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
We previously observed that genistein induces apoptosis and inhibits growth and prostate-specific antigen (PSA) production and secretion in androgen-dependent (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. To determine the effect of soy isoflavones on serum PSA levels, we conducted a phase II clinical trial in patients with prostate cancer. Eligible patients had prostate cancer and were previously untreated (group I), treated with local therapy (group II), or treated with hormone therapy (group III) and had to have either three successive measurements of rising PSA levels or a PSA of >10 mg/L (294 pmol/L) at two successive evaluations. No other therapy or micronutrient supplements were allowed. Patients received 100 mg soy isoflavones orally twice daily for a minimum of 3 mo in the absence of progression or toxicity. Serum levels of total genistein and daidzein, PSA, testosterone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured and
toxicity was assessed monthly. Forty-one patients were enrolled; 4 patients in group I, 18 in group II, and 19 in group III, with a median PSA level of 13.3 mg/L (391 pmol/L). Forty patients were evaluated for PSA response. A total of 226 mo of supplementation was given with a median of 6 mo per patient (range 1–10 mo). Three of 4 patients in group I, 15 of 18 in group II, and 6 of 19 in group III achieved stable disease. The rate of linear rise in serum PSA levels decreased by 71% (from 14% to 4%, P = 0.03) in group II and by 56% (from 27% to 16%, P = 0.07) in group III patients. Although significant increases in serum isoflavones were observed after supplementation, no significant changes were observed in serum levels of testosterone, insulin-like growth factor-1, or 5-hydroxy-methyl-deoxyuridine. Interestingly, insulin-like growth factor binding protein-3 level decreased significantly after soy isoflavone supplementation (P = 0.0007). Although the mechanism is unclear, soy isoflavones appear to decrease the rate of rise in serum PSA and stabilize the disease in patients with hormone-sensitive as well as hormonerefractory prostate cancer.
Soy Isoflavones in the Treatment of Prostate Cancer.
Maha Hussain1, Fazlul H. Sarkar2, Zora Djuric1, Michael N. Pollak3, Mousumi Banerjee4, Daniel Doerge5, Joseph Fontana1,6, Sreenivasa Chinni2, Joanne Davis2, Jeffrey Forman7, David P. Wood8, and Omer Kucuk1,
1Division of Hematology and Oncology,
2Department of Pathology, 7Department of Radiation Oncology, 8Department of Urology, and 4Center for Healthcare Effectiveness Research, Wayne State University and the Barbara Ann Karmanos Cancer Institute, 3990 John R Street, Detroit, MI 48201, USA; 6VA Medical Center, Detroit, MI; 3Department of Medicine, McGill University and Jewish General Hospital, Montreal, Quebec, Canada; 5Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.
We previously observed that genistein induces apoptosis and inhibits growth and prostate-specific antigen (PSA) production and secretion in androgen-dependent (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. To determine the effect of soy isoflavones on serum PSA levels, we conducted a phase II clinical trial in patients with prostate cancer. Eligible patients had prostate cancer and were previously untreated (group I), treated with local therapy (group II), or treated with hormone therapy (group III) and had to have either three successive measurements of rising PSA levels or a PSA of >10 mg/L (294 pmol/L) at two successive evaluations. No other therapy or micronutrient supplements were allowed. Patients received 100 mg soy isoflavones orally twice daily for a minimum of 3 mo in the absence of progression or toxicity. Serum levels of total genistein and daidzein, PSA, testosterone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured and
toxicity was assessed monthly. Forty-one patients were enrolled; 4 patients in group I, 18 in group II, and 19 in group III, with a median PSA level of 13.3 mg/L (391 pmol/L). Forty patients were evaluated for PSA response. A total of 226 mo of supplementation was given with a median of 6 mo per patient (range 1–10 mo). Three of 4 patients in group I, 15 of 18 in group II, and 6 of 19 in group III achieved stable disease. The rate of linear rise in serum PSA levels decreased by 71% (from 14% to 4%, P = 0.03) in group II and by 56% (from 27% to 16%, P = 0.07) in group III patients. Although significant increases in serum isoflavones were observed after supplementation, no significant changes were observed in serum levels of testosterone, insulin-like growth factor-1, or 5-hydroxy-methyl-deoxyuridine. Interestingly, insulin-like growth factor binding protein-3 level decreased significantly after soy isoflavone supplementation (P = 0.0007). Although the mechanism is unclear, soy isoflavones appear to decrease the rate of rise in serum PSA and stabilize the disease in patients with hormone-sensitive as well as hormonerefractory prostate cancer.
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