Inhibition of orthotopic growth and metastasis of androgen‐sensitive human prostate tumors in mice by bioactive soybean components

Zhou, Jin‐Rong; Yu, Lunyin; Zhong, Ying; Nassr, Rena L.; Franke, Adrian A.; Gaston, Sandra M.; Blackburn, George L.

doi:10.1002/pros.10141

Cited by 79 publications

(72 citation statements)

References 25 publications

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“…15,[21][22][23][24] Feeding mice with soy phytochemical concentrate (SPC, containing genistein, daidzein and glycitein) or an aglycone isoflavone preparation reduced tumor growth of s.c. implanted human LNCaP cells in immunocompromised mice. 15,22 In a prevention study of Zhou et al, 23 using an orthotopic model of LNCaP cells in SCID mice similar to our model, SPC was more effective than genistein or soy protein. This prevention study is in agreement with the efficacy demonstrated by soy isoflavones in our therapeutic study of established prostate tumors.…”

Section: Discussionmentioning

confidence: 99%

Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model

Raffoul

Banerjee

Che

et al. 2007

Intl Journal of Cancer

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We previously reported that genistein, the bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer. Pretreatment of tumor cells with genistein potentiated radiation-induced killing in vitro and in orthotopic models in vivo. However, pure genistein promoted increased lymph node metastasis, when administered alone in vivo. We investigated in vitro and in vivo the effects of soy isoflavones (genistein, daidzein and glycitein) as soy pills of similar composition are used in human interventions but not pure genistein. Soy isoflavones inhibited cell survival and potentiated radiation cell killing in PC-3 tumor cells, in vitro. Increased cell killing correlated with inhibition of antiapoptotic molecules Bcl-xL and survivin, upregulation of proapoptotic Bax molecule and PARP cleavage, suggesting activation of apoptotic pathways. In vivo, using the PC-3 orthotopic metastatic mouse model, soy isoflavones and prostate tumor irradiation led to enhanced control of primary tumor growth and metastasis, as observed with pure genistein and radiation. Interestingly, treatment with soy isoflavones did not increase metastasis to para-aortic lymph nodes in contrast to the consistent increase caused by pure genistein. Histologically prostate tumors, treated with soy isoflavones and radiation, showed tumor destruction and in situ tissue alterations, comparable with genistein and radiation effects. However, genistein, but not soy isoflavones, caused induction of HIF1-a in prostate tumors, suggesting that induction of hypoxia by pure genistein could contribute to increased metastasis. Our studies demonstrate the safety and potential role of soy isoflavones for enhancing the therapeutic effect of radiotherapy in prostate cancer. ' 2007 Wiley-Liss, Inc.Key words: prostate cancer; soy isoflavones; genistein; radiation In the United States, prostate cancer (PCa) is the most commonly diagnosed cancer in men as well as the second leading cause of male cancer deaths. 1,2 Localized PCa is sensitive to conventional radiotherapy using megavoltage photons (X-rays), yet residual disease causes clinical relapse. 2 Thus, for improving the local control of PCa, the combination of radiation with additional antitumor agents is warranted. Epidemiological studies indicate that there is an inverse association between prostate cancer risk and consumption of phytoestrogens including isoflavones. [3][4][5] The isoflavones in soybeans mainly include genistein, daidzein and glycitein. 5 Genistein, the most bioactive isoflavone, has demonstrated inhibition of tumor cell growth in human tumor cell lines. 5 In particular, genistein inhibited the growth of human PCa cells in vitro by affecting the cell cycle and inducing apoptosis. 5 To improve the therapeutic efficacy of radiotherapy for prostate cancer, we have previously investigated the potential of genistein to act as a radiosensitizer. 6-9 Genistein significantly increased tumor cell death when given prior to radiation in several human cancer cell lines in vitro, including the PC-3 PCa...

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Section: Discussionmentioning

confidence: 99%

Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model

Raffoul

Banerjee

Che

et al. 2007

Intl Journal of Cancer

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“…Growth inhibition and induction of apoptosis of prostate cancer cells by isoflavones were indicated in several experimental reports. [16][17][18][19][20][21][22][23][24][25] Tofu and natto are rich in isoflavones (tofu 509 µg/g and natto 1273 µg/g 26) ). In fact, Japanese have higher phytoestrogen concentrations in serum than men and women of Western countries (for example, the mean concentration of genistein in phytoestrogen in Japanese men is 492.7 nmol/liter, compared with 33.2 nmol/liter in men from the UK), 27) and have very high urinary excretion of phytoestrogens.…”

Section: Discussionmentioning

confidence: 99%

A case‐control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet

et al. 2004

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The age-adjusted incidence of prostate cancer is low in Japan, and it has been suggested that the traditional Japanese diet, which includes many soy products, plays a preventive role against prostate cancer. We performed a case-control study on dietary factors and prostate cancer in order to assess the hypothesis that the traditional Japanese diet reduces the risk of prostate cancer. Four geographical areas (Ibaraki, Fukuoka, Nara, and Hokkaido) of Japan were selected for the survey. Average daily intake of food from 5 years before the diagnosis was measured by means of a semi-quantitative food frequency questionnaire. We studied 140 cases and 140 individually age ( ± ± ± ±5 years)-matched hospital controls for analysis. Estimates of age-adjusted odds ratios (ORs) and linear trends were calculated by conditional logistic regression models with adjustment for cigarette smoking and total energy intake as confounding factors. Consumption of fish, all soybean products, tofu (bean curds), and natto (fermented soybeans) was associated with decreased risk. ORs of the fourth vs. first quartile and 95% confidence intervals (95%CIs) were 0.45 (0.20-1.02) for fish, 0.53 (0.24-1.14) for all soybean products, 0.47 (0.20-1.08) for tofu, and 0.25 (0.05-1.24) for natto. Consumption of fish and natto showed significantly decreasing linear trends for risk (P < < < <0.05). Consumption of meat was significantly associated with increased risk (the OR of the second vs. first quartile was 2.19, 95%CI 1.00-4.81). Consumption of milk, fruits, all vegetables, green-yellow vegetables, and tomatoes showed no association. Our results provide support to the hypothesis that the traditional Japanese diet, which is rich in soybean products and fish, might be protective against prostate cancer. (Cancer Sci 2004; 95: 238-242) he age-standardized incidence of prostate cancer is low in Japan (10.0 per 100,000), being approximately one-tenth of that in the United States.1) Among Japanese immigrant in Hawaii, age-standardized incidence of prostate cancer is approximately ten times that in Japan.2) It is suggested that environmental factors such as dietary habits play a major role in causation of prostate cancer. A number of case-control studies have indicated that high intake of fat, especially saturated fat, increases the risk of prostate cancer.3) In contrast, high intake of isoflavone, which is mainly found in soybeans and soy products, may reduce the risk of prostate cancer. 4,5) The traditional Japanese diet which includes many soy products is richer in isoflavone, 6,7) and contains less fat than the Western diet. However, an epidemiological study of prostate cancer in Kyoto in 1988 8) yielded no evidence that fat or soybeans were associated with the risk of prostate cancer.Recently in Japan, the incidence rate of prostate cancer has been increasing cocomitantly with the westernization of dietary habits. We carried out a case-control study on dietary factors and prostate cancer to assess the hypothesis that the traditional Japanese diet reduc...

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“…The use of soy in Asian diets is theorized to be one of the reasons for the low incidence and mortality rates from prostate cancer in Asian men, which are rapidly increasing with the Westernization 60 of their traditional diet (17). This hypothesis is supported by findings from both laboratory and animal studies, indicating an anti-proliferative and apoptotic effect in cancer cells of isoflavones, the phytoestrogens present in soy (18)(19)(20)(21). However, epidemiological and clinical investigations on the 65 role of soy protein in relation to IGF-I suggest that soy protein may alter the IGF axis toward an increase in IGF-1 and a reduction in IGFBP-3 (22)(23)(24)(25)(26).…”

Section: Protein (58 G/day) After One Year Intervention Group Patiementioning

confidence: 99%

“…In addition, the correlations performed at one year confirmed the positive association between IGFBP-1 405 and vegetable protein, and also showed a positive association with soy isoflavones. Furthermore, both vegetable protein and soy isoflavones were inversely related to LNCaP cell growth, suggesting that consumption of vegetable protein and isoflavones may be beneficial against tumor growth (18)(19)(20). 410 Our study is limited by the post-hoc design, which did not allow us to analyze the relationship of dietary protein and isoflavones alone to the IGF axis.…”

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confidence: 99%