Anticancer effects of daidzein, genistein and soy extracts on human prostate cancer cells

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University of Delaware
Prostate cancer is one of the most common cancers in men. However, the incidence of clinical prostate cancer varies widely between ethnic populations and countries. Epidemiological studies have shown that higher intake of soy foods can lower risk of prostate cancer. Soy isoflavones, such as daidzein, genistein, and their sugar conjugates, daidzin and genistin, are considered to be major bioactive compounds in soy and provide chemoprotection of prostate cancer. The majority of studies to assess the anticancer efficacy of soy products for prostate cancer (PCa) have been performed using purified bioactive compounds such as daidzein and genistein at pharmacological concentrations for short periods using androgen independent PCa cells such as PC-3 or androgen sensitive PCa cells such as LNCaP. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans and the limited effect of individual soy isoflavones and these studies cannot reflect the real effects that soy may induce through diets. Currently, little is known about the bioavailability of isoflavones from whole soy foods and their bioactivities after cooking and digestion. The objectives of this study include: 1) examine the antiproliferative and apoptotic effects of high-dose (25 to 200 μM) individual soy isoflavones, daidzein and genistein, using two human prostate cancer cell lines, LNCaP and C4-2B, from the LNCaP progression model and explore the possible synergistic effects of the two isoflavones; 2) study the effects of low-dose (serum level), long-term exposure to daidzein and genistein on proliferation, apoptosis and cell cycle of LNCaP prostate cancer cells; 3) determine the antioxidant activities, isoflavone contents, antiproliferative and apoptotic effects on LNCaP and C4-2B human prostate cancer cells of extracts from whole soybeans and investigate the effects of heating and in vitro digestion on their bioactivities. In the study of acute effects of high-dose isoflavones, significant apoptotic and antiproliferative effects were observed on both LNCaP and C4-2B cells. Daidzein and genistein showed a synergistic effect on inhibiting prostate cancer cell proliferation and inducing apoptosis. The low-dose long-term treatment did not change the proliferation and apoptosis of LNCaP cells significantly. However, the treatment with 250 nM daidzein reduced the effectiveness of docetaxel, a clinical chemotherapy drug, and all the three treatments had significant impact on LNCaP cell cycle progression. To evaluate the anticancer effects of soy food intake, we stimulated food intake by performing cooking and in vitro digestion process on whole soy. It turned out that after cooking and in vitro digestion, antioxidant activities of soy extracts increased while no consistent increase of the contents of four soy isoflavones was found. Better apoptotic effects on both LNCaP and C4-2B cells were found in cooked and digested soy extracts when compared with purified individual isoflavones, which indicated synergistic interactions between various bioactive compounds in whole soy foods. Our study is the first study that investigated the effects of low-dose, long-term treatment of soy isoflavones on prostate cancer cells, evaluated the impact of low-dose, long-term exposure to soy isoflavones on the potency of docetaxel. Compared to other studies, we first used cooking and in vitro digestion to prepare soy extracts and examined the effects of cooking and digestion on the bioactivities of the whole soy exacts, thus it is more comparable to real ingestion of whole food by humans, and can provide more and better information for the preventive and therapeutic effects of soy food consumptions on prostate cancers.
Soy isoflavene