Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application

Wang, Zhijun; Fan, Jianhui; Liu, Mandy; Yeung, Steven; Chang, Andy; Chow, Moses S. S.; Pon, Doreen; Huang, Ying

doi:10.1517/13543784.2013.833183

Cited by 27 publications

(13 citation statements)

References 104 publications

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“…Prostate cancer is an ideal disease for chemoprevention due to its high incidence rate, long course and slow progression (101). It has been widely recognized that men in the United States and other Western countries suffer from a higher incidence rate of prostate cancer than ones living in Eastern countries (102).…”

Section: Chemopreventive Effects and Relevant Mechanismsmentioning

confidence: 99%

Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review)

Yang

Song

Wang³

et al. 2015

Oncology Reports

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The morbidity and mortality of prostate cancer have been increasing recently, and the comprehensive treatment for prostate cancer is unable to achieve satisfactory outcomes. Quercetin is a natural flavonoid compound that has attracted increased interest and attention due to its anticancer activity. In vitro and in vivo studies have verified that quercetin effectively inhibits prostate cancer via various mechanisms. Clinical trails concerning the pharmacokinetics and application of quercetin in humans have also obtained promising results. Meanwhile, epidemiologic studies have demonstrated a negative association between quercetin intake and prostate cancer incidence and have suggested a chemopreventive effect of quercetin on prostate cancer that has been exhibited in animal experiments. The main issue concerning quercetin utilization is its low bioavailability. Therefore, solutions to the issues concerning its use such as alteration of the molecular structure and combination therapy are in the exploratory stage. In the present review, the most important aspects of chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential of quercetin in prostate cancer are summarized.

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Section: Chemopreventive Effects and Relevant Mechanismsmentioning

confidence: 99%

Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review)

Yang

Song

Wang³

et al. 2015

Oncology Reports

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“…Drugs targeting the enzymes responsible for epigenetic silencing, such as 5-azadeoxycytidine (5-aza, a DNMT inhibitor) (14) and trichostatin A (TSA, an HDAC inhibitor), have been widely investigated as cancer therapeutic agents. In addition to Western drugs, phytochemicals have also been found to possess chemoprevention effects via epigenetic alterations (15). For example, mahanine, a carbazole alkaloid found abundantly in some Asian vegetables, has been reported to be a DNA hypomethylation agent that restored the expression of an epigenetically silenced tumor suppressor gene due to the inhibitory effect of DNMTs (16).…”

Section: Introductionmentioning

confidence: 99%

Blocking of JB6 Cell Transformation by Tanshinone IIA: Epigenetic Reactivation of Nrf2 Antioxidative Stress Pathway

Wang

Zhang

Guo

et al. 2014

AAPS J

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Abstract. Increasing numbers of natural products have been found to possess anticancer effects. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator of the antioxidative stress response, and our previous studies found that epigenetic modification of the Nrf2 gene appears to be a critical mechanism. Salvia miltiorrhiza, a Chinese herbal medicine widely used in Asian countries, has been shown to possess anticancer and antioxidant effects. Tanshinone IIA (TIIA), an active component in S. miltiorrhiza, has been reported to activate Nrf2 pathway. The objective of this study was to investigate the epigenetic regulation of Nrf2 by TIIA in mouse skin epidermal JB6 cells and the functional consequences for cell transformation. TIIA was found to induce antioxidant response element-luciferase and upregulate the mRNA and protein levels of Nrf2 and Nrf2 downstream target genes HO-1 and NQO-1. TIIA decreased the colony formation of JB6 cells by approximately 80%. TIIA decreased the protein levels of DNMT1, DNMT3a, DNMT3b, and HDAC3 and inhibited the enzymatic activity of HDACs. Bisulfite genomic sequencing indicated that TIIA demethylated the first five CpGs in the promoter region of the Nrf2 gene. Chromatin immunoprecipitation assays showed that TIIA treatment increased the recruitment of RNA polymerase II at Nrf2 transcription start site but had limited effects on enrichment of Ac-H3 in Nrf2 promoter. Taken together, our results show that TIIA activates the Nrf2 signaling pathway and induces epigenetic demethylation of the CpGs of Nrf2. The epigenetic reactivation of the Nrf2 signaling pathway by TIIA could potentially contribute to the attenuation of JB6 cellular transformation and anticancer effects.

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“…One of the most exciting strategies to reduce the burden of prostate cancer is the use of chemopreventive agents ( Ratan et al ., 2002 ; Bommareddy et al ., 2013 ; Wang et al ., 2013 ). Resveratrol (3,5,4′-trihydroxy- trans -stilbene), a phytoalexin ab undantly present in grapes and other medicinal plants, has been extensively investigated for its chemopreventive and chemotherapeutic potential ( Shankar et al ., 2007 ; Kundu and Surh, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells

Lee

Kundu

Keum

et al. 2014

Biomolecules & Therapeutics

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Prostate cancer is the most frequently diagnosed cancer. Although prostate tumors respond to androgen ablation therapy at an early stage, they often acquire the potential of androgen-independent growth. Elevated transcriptional activity of androgen receptor (AR) and/or signal transducer and activator of transcription-3 (STAT3) contributes to the proliferation of prostate cancer cells. In the present study, we examined the effect of resveratrol, a phytoalexin present in grapes, on the reporter gene activity of AR and STAT3 in human prostate cancer (LNCaP-FGC) cells stimulated with interleukin-6 (IL-6) and/or dihydrotestosterone (DHT). Our study revealed that resveratrol suppressed the growth of LNCaP-FGC cells in a time- and concentration-dependent manner. Whereas the AR transcriptional activity was induced by treatment with either IL-6 or DHT, the STAT3 transcriptional activity was induced only by treatment with IL-6 but not with DHT. Resveratrol significantly attenuated IL-6-induced STAT3 transcriptional activity, and DHT- or IL-6-induced AR transcriptional activity. Treatment of cells with DHT plus IL-6 significantly increased the AR transcriptional activity as compared to DHT or IL-6 treatment alone and resveratrol markedly diminished DHT plus IL-6-induced AR transcriptional activity. Furthermore, the production of prostate-specific antigen (PSA) was decreased by resveratrol in the DHT-, IL-6- or DHT plus IL-6-treated LNCaP-FGC cells. Taken together, the inhibitory effects of resveratrol on IL-6- and/or DHT-induced AR transcriptional activity in LNCaP prostate cancer cells are partly mediated through the suppression of STAT3 reporter gene activity, suggesting that resveratrol may be a promising therapeutic choice for the treatment of prostate cancer.

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Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application

Cited by 27 publications

References 104 publications

Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review)

Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review)

Blocking of JB6 Cell Transformation by Tanshinone IIA: Epigenetic Reactivation of Nrf2 Antioxidative Stress Pathway

Resveratrol Inhibits IL-6-Induced Transcriptional Activity of AR and STAT3 in Human Prostate Cancer LNCaP-FGC Cells

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