The Prevention of Prostate Cancer

Griffiths, K.; Prezioso, Domenico; Turkes, A.; Denis, L.

doi:10.1007/978-3-540-40901-4_4

Cited by 12 publications

(9 citation statements)

References 155 publications

(160 reference statements)

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“…Most prostate tumors take a period of about 20-25 years to develop from a focal lesion to clinically detectable phenotype, and many patients die with prostate cancer without any symptoms 2 . However, there are cases of aggressive prostate cancer that metastasize rapidly particularly to the bones and lymph nodes, often before symptoms are noticed 3 .…”

Section: Introductionmentioning

confidence: 99%

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

Wang

Solorzano

Diaz

et al. 2017

Clinical Nutrition Experimental

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The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (< 2μM) significantly inhibited the proliferation of LNCaP and LAPC-4 cells by 30-50% at 48h compared to control, and inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial cells. Male severe combined immunodeficiency (SCID) mice were implanted subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the intervention started one week after tumor implantation. Mice received arctigenin at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo, which provides a high promise in its translation to human application.

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Section: Introductionmentioning

confidence: 99%

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

Wang

Solorzano

Diaz

et al. 2017

Clinical Nutrition Experimental

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“…Indeed, prostate carcinogenesis is considered an ideal candidate for chemoprevention due to the long latency period and slow disease progression, which provides an opportunity to intervene before the malignancy is established, thus delaying progression and improving quality of life of the patients (Syed et al 2007;Stephenson et al 2010). Many observational and intervention studies have been conducted using vitamins, phytochemicals and minerals as chemoprotective compounds (Griffiths et al 2007). The use of vitamin E as a chemoprotective agent against PCa is based upon the ability of vitamin E to scavenge free radicals and prevent oxidative damage to the prostate epithelium (Campbell et al 2011).…”

mentioning

confidence: 99%

Protective effect of γ‐tocopherol‐enriched diet on N‐methyl‐N‐nitrosourea‐induced epithelial dysplasia in rat ventral prostate

Sanches

Santos

Carvalho

et al. 2013

Int J Experimental Path

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Despite recent advances in understanding the biological basis of prostate cancer (PCa), the management of this disease remains a challenge. Chemoprotective agents have been used to protect against or eradicate prostate malignancies. Here, we investigated the protective effect of γ-tocopherol on N-methyl-N-nitrosourea (MNU)-induced epithelial dysplasia in the rat ventral prostate (VP). Thirty-two male Wistar rats were divided into four groups (n = 8): control (CT): healthy control animals fed a standard diet; control+γ-tocopherol (CT+γT): healthy control animals without intervention fed a γ-tocopherol-enriched diet (20 mg/kg); N-methyl-N-nitrosourea (MNU): rats that received a single dose of MNU (30 mg/kg) plus testosterone propionate (100 mg/kg) and were fed a standard diet; and MNU+γ-tocopherol (MNU+γT): rats that received the same treatment of MNU plus testosterone and were fed with a γ-tocopherol-enriched diet (20 mg/kg). After 4 months, the VPs were excised to evaluate morphology, cell proliferation and apoptosis, as well as cyclooxygenase-2 (Cox-2), glutathione-S-transferase-pi (GST-pi) and androgen receptor (AR) protein expression, and matrix metalloproteinase-9 (MMP-9) activity. An increase in the incidence of epithelial dysplasias, such as stratified epithelial hyperplasia and squamous metaplasia, in the MNU group was accompanied by augmented cell proliferation, GST-pi and Cox-2 immunoexpression and pro-MMP-9 activity. Stromal thickening and inflammatory foci were also observed. The administration of a γ-tocopherol-enriched diet significantly attenuated the adverse effects of MNU in the VP. The incidence of epithelial dysplasia decreased, along with the cell proliferation index, GST-pi and Cox-2 immunoexpression. The gelatinolytic activity of pro-MMP-9 returned to the levels observed for the CT group. These results suggest that γ-tocopherol acts as a protective agent against MNU-induced prostatic disorders in the rat ventral prostate.

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“…LADY mice, rapidly developed massive prostatic hyperplasia within a few months. Human primary prostate cancer, on the other hand, is slow growing in most cases [55,56]. We surmise that the effects of TSPY might not be readily noticeable in fast-growing tumor developed in the LADY mouse background.…”

Section: Discussionmentioning

confidence: 97%

Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer

et al. 2014

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BackgroundThe human TSPY is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that TSPY is a Y-located proto-oncogene contributing to the initiation/progression in human cancers, including germ cell tumors and various somatic cancers, such as prostate and liver cancer, and melanoma. The TgTSPY9 transgenic mouse line harbors a 8.2-kb human TSPY structural gene, which is tandemly integrated in the mouse Y chromosome, and expressed in a similar pattern as that of the endogenous gene in the human genome. This mouse model of human TSPY gene offers an opportunity to examine its behavior and potential contribution in various mouse models of human diseases, such as human cancers. We had investigated the expression of such TSPY-transgene in the LADY mouse model of prostate cancer, harboring a SV40 T antigen gene directed by a rat probasin promoter; and compared the expression pattern with those of endogenous TSPY gene and biomarkers in human prostate cancer specimens.ResultsBy introducing the Y-located TSPY-transgene to the LADY mice, we had examined the expression pattern of the human TSPY during prostatic oncogenesis in this mouse model of prostate cancer. Our results showed that the TSPY-transgene was activated in selected areas of the hypercellular stroma but not in the intraepithelial cells/neoplasia in the prostates of TgTSPY9/LADY mice. Using a specific biomarker, FOXA1, for epithelial cells, we demonstrated that TSPY-positive cells proliferated exclusively in the cancerous stroma in the LADY model at late stages of tumorigenesis. In contrast, in the human situation, TSPY was predominantly co-expressed with FOXA1 in the epithelial cells of PIN lesions and FOXA1 and another cancer biomarker, AMACR, in the adenocarcinoma cells in clinical prostate cancer samples of various degrees of malignancy.ConclusionsOur data show that human TSPY could be abnormally activated during prostatic oncogenesis, and could possibly contribute to the heterogeneity of prostate cancer. The differential expression patterns of the human TSPY between the LADY mouse model and clinical prostate cancer suggest potential limitations of current mouse models for studies of either TSPY behavior in diseased conditions or prostate cancer development.

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The Prevention of Prostate Cancer

Cited by 12 publications

References 155 publications

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

Protective effect of γ‐tocopherol‐enriched diet on N‐methyl‐N‐nitrosourea‐induced epithelial dysplasia in rat ventral prostate

Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer

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