Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture

Geller, Jack; Sionit, Lida; Partido, Christine; Li, Lingna; Tan, Xiuying; Youngkin, Tyler; Nachtsheim, Daniel A.; Hoffman, Robert M.

doi:10.1002/(sici)1097-0045(19980201)34:2<75::aid-pros1>3.0.co;2-i

Cited by 84 publications

(17 citation statements)

References 11 publications

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“…Genestein is an isoflavonoid found in soybeans, and is present in high levels in the traditional Japanese and Chinese diets [175]. Genistein is a phytoestrogen, which affects both estrogen and androgen signaling pathways.…”

Section: Therapies Hormones and Bphmentioning

confidence: 99%

“…Japanese and Chinese men also have lower rates of BPH than observed in Western populations, and given the importance of estrogen and androgen signaling in BPH, some studies have examined the potential for soy isoflavones in prevention and treatment strategies for BPH. Treatment of BPH cells derived from TURP specimens with genistein versus vehicle control revealed that genistein inhibits the growth of BPH cells in culture in a dose-dependent manner [175]. Using benign prostate epithelial cells (BPH-1), Hsu et al showed that the soy isoflavones genistein and Daizein induced apoptosis [177].…”

Section: Therapies Hormones and Bphmentioning

confidence: 99%

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Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

2011

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Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens and androgen receptor pathways to BPH and use of androgen reducing compounds, such as 5α-reductase inhibitors which block the conversion of testosterone into dihydrotestosterone, are a component of the standard of care for men with LUTS attributed to an enlarged prostate. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17β. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; however, new models are needed to genetically dissect estrogen regulated molecular mechanisms involved in BPH. More work is needed to identify estrogens and associated signaling pathways in BPH in order to target BPH with dietary and therapeutic SERMs.

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Section: Therapies Hormones and Bphmentioning

confidence: 99%

Section: Therapies Hormones and Bphmentioning

confidence: 99%

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

2011

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“…Moreover, others have shown that the anticancer effect of gensitein is dependent on the ER α /ER β ratio, where gensitein is estrogenic at high ER α concentrations, as may be the case with the MCF-7 cell line (71,72). Genistein has also been shown to inhibit the growth of cancer cells using a 3-D gel culture system, which is more physiologically relevant than the 2-D culture approach of the present study (73,74). …”

Section: Discussionmentioning

confidence: 67%

Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein

Parra

Castillo‐Pichardo

Cruz-Collazo

et al. 2016

Nutrition and Cancer

107

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We previously reported that dietary genistein inhibits mammary tumor growth and metastasis of the highly metastatic MDA-MB-435 cancer cells in immunocompromised mice. The purpose herein was to characterize the role of the novel oncogenic microRNA (miRNA) miR-155 in the anticancer effects of genistein in metastatic breast cancer. The effect of genistein was determined on breast cancer cell viability, apoptosis, and expression of miR-155 and its targets. At low physiologically relevant concentrations, genistein inhibits cell viability and induces apoptosis in metastatic MDA-MB-435 and Hs578t breast cancer cells, without affecting the viability of nonmetastatic MCF-7 breast cancer cells. In parallel with reduced cell viability, miR-155 is downregulated, whereas proapoptotic and anticell proliferative miR-155 targets FOXO3, PTEN, casein kinase, and p27 are upregulated in MDA-MB-435 and Hs578t cells in response to genistein treatment. However, miR-155 levels remain unchanged in response to genistein in the MCF-7 cells. Ectopic expression of miR-155 in MDA-MB-435 and Hs578t cells decreases the effects of genistein on cell viability and abrogates the effects of genistein on apoptosis and expression of proapoptotic genes. Therefore, genistein-mediated downregulation of miR-155 contributes to the anticancer effects of genistein in metastatic breast cancer.

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“…In humans, prostate cancer patients who consumed high levels of phytoestrogens had lower levels of prostate-specific antigen, a common marker for prostate cancer [6, 13]. In addition, organ culture studies showed that the phytoestrogen genistein decreased growth of prostate cancer tissue and benign prostatic hypertrophy [14–16]. Taken together, these studies suggest that some constituent of phytoestrogen-containing diets possesses antiandrogenic and antitumorogenic activities, which could provide some beneficial effects in prostate cancer patients [17].…”

Section: Introductionmentioning

confidence: 99%

Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

Solipuram

Koppula

Hurst

et al. 2009

Journal of Toxicology

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The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea “Bizzy,” using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

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Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture

Cited by 84 publications

References 11 publications

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

Androgens and estrogens in benign prostatic hyperplasia: Past, present and future

Soy Isoflavone Genistein-Mediated Downregulation of miR-155 Contributes to the Anticancer Effects of Genistein

Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

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