The epigenetic potentials of dietary polyphenols in prostate cancer management

Abbas, Ata; Patterson, William L.; Georgel, Philippe

doi:10.1139/bcb-2012-0044

Cited by 23 publications

(14 citation statements)

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“…Prostate cancer (PCa) is the second most common cause of cancer-related death in men in the USA because of advanced castrate-resistant disease and associated metastasis. Since the incidence of this slow growing cancer is very high and diet is an associated risk factor [1], efforts have been driven toward the development of chemopreventive strategies with the use of natural bioactive compounds [2][3][4]. Our group has shown that stilbenes, particularly resveratrol and pterostilbene found in grapes and blueberries, have targeted chemo-protective effects against PCa in vitro and in vivo [5][6][7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

et al. 2017

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The metastasis‐associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression‐related epigenetic regulator, which is overexpressed in hormone‐refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate‐specific Pten‐null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo. We generated and utilized a luciferase reporter in a prostate‐specific Pten‐null mouse model (Pb‐Cre +; Pten f/f; Rosa26 Luc/+) to evaluate the anticancer efficacy of Pter/SAHA combinatorial approach. Our data showed that Pter sensitized tumor cells to SAHA treatment resulting in inhibiting tumor growth and additional decline of tumor progression. These effects were dependent on the reduction of MTA1‐associated proangiogenic factors HIF‐1α, VEGF, and IL‐1β leading to decreased angiogenesis. In addition, treatment of PCa cell lines in vitro with combined Pter and low dose SAHA resulted in more potent inhibition of MTA1/HIF‐1α than by high dose SAHA alone. Our study provides preclinical evidence that Pter/SAHA combination treatment inhibits MTA1/HIF‐1α tumor‐promoting signaling in PCa. The beneficial outcome of combinatorial strategy using a natural agent and an approved drug for higher efficacy and less toxicity supports further development of MTA1‐targeted therapies in PCa.

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Section: Introductionmentioning

confidence: 99%

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

et al. 2017

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“…Lifestyle factors, such as diet and nutrition, play a significant role in the pathogenesis of PCa, and multiple studies have revealed that intensive nutrition and lifestyle changes might modulate gene expression in the prostate. These findings highlight the potential role of dietary phytochemicals in the treatment of PCa[3–5]. Studies evaluating epigenetic modifications in cancer, specifically those that lead to the inactivation or silencing of key regulatory genes, such as tumor suppressor genes, has led to the realization that genetic and epigenetic changes play a critical role in tumorigenesis[6].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells

Boyanapalli

Fuentes

et al. 2016

Pharmacological Research

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Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive. The present study aimed to examine the role of PEITC in the epigenetic reactivation of RASSF1A and the induction of apoptosis in LNCaP cells. LNCaP cells were treated for 5 days with 0.01% DMSO, 2.5 or 5 μM PETIC or 2.5 μM azadeoxycytidine (5-Aza) with 0.5 μM trichostatin A (TSA). We evaluated the effects of these treatments on CpG demethylation using methylation-specific polymerase chain reaction (MSP) and bisulfite genomic sequencing (BGS). CpG demethylation was significantly enhanced in cells treated with 5 μM PEITC and 5-Aza+TSA; therefore, the latter treatment was used as a positive control in subsequent experiments. The decrease in RASSF1A promoter methylation correlated with an increase in expression of the RASSF1A gene in a dose-dependent manner. To confirm that promoter demethylation was mediated by DNA methyltransferases (DNMTs), we analyzed the expression levels of DNMTs and histone deacetylases (HDACs) at the gene and protein levels. PEITC reduced DNMT1, 3A and 3B protein levels in a dose-dependent manner, and 5 μM PEITC significantly reduced DNMT3A and 3B protein levels. HDAC1, 2, 4 and 6 protein expression was also inhibited by 5 μM PEITC. The combination of 5-Aza and TSA, a DNMT inhibitor and a HDAC inhibitor, respectively, was used as a positive control as this treatment significantly inhibited both HDACs and DNMTs. The function of RASSF1A reactivation in promoting apoptosis and inducing G2/M cell cycle arrest was analyzed using flow-cytometry analysis with Annexin V and propidium iodide (PI). Growth inhibition effect on LNCaP cells were investigated by colony formation assay. In addition, we analyzed p21, caspase-3 and 7, Bax, and Cyclin B1 protein levels. Flow-cytometry analysis of cells stained with PI alone demonstrated that 5 μM PEITC promotes early apoptosis and G2/M cell cycle arrest. Flow cytometry analysis of cells stained with Annexin V and PI also demonstrated an increased proportion of cells in early apoptosis in cells treated with 5 μM PEITC or 5-Aza with TSA. PEITC and efficiently inhibit colony numbers and total area. In addition, 5 μM PEITC significantly enhanced p21, caspase-3, 7 and Bax levels and reduced Cyclin B1 expression compared with the control group. Collectively, the results of our study suggest that PEITC induces apoptosis in LNCaP cells potentially by reactivating RASSF1A via epigenetic mechanisms.

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“…The tea plant (Camellia sinensis) has been cultivated in Asia for thousands of years and green tea has been used for centuries in China, Japan, and Thailand as a traditional medicine with a variety of applications (Abbas et al 2013). Over the last two decades, many epidemiological studies have evaluated the chemopreventive properties of green tea, suggesting that increasing intake of green tea is correlated with significant decrease in the development of prostate cancer.…”

Section: Epigallocatechin-3-gallatementioning

confidence: 99%

Pharmacological Role of Dietary Polyphenols in Prostate Cancer Chemoprevention

Cimino

Russo

Reale

et al. 2016

Critical Dietary Factors in Cancer Chemoprevention

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Prostate cancer (PCa) is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable pre-neoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds of dietary origin are available on the market and certainly polyphenols such as epigallocatechin-3-gallate, curcumin, resveratrol, and the flavonoids quercetin and genistein represent those with supposed efficacy against PCa. As shown by many reports on PCa, the use of natural compounds could act against oxidative stress chronic inflammation. Basic research studies have revealed that polyphenols appear to act not only against oxidative stress but also impede pro-neoplastic cancer cell signaling. Although the current studies are limited, mechanisms of action of polyphenols have been confirmed, showing a promising future strategy in prostate cancer chemoprevention.

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The epigenetic potentials of dietary polyphenols in prostate cancer management

Cited by 23 publications

References 54 publications

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

Targeting MTA1/HIF‐1α signaling by pterostilbene in combination with histone deacetylase inhibitor attenuates prostate cancer progression

Epigenetic reactivation of RASSF1A by phenethyl isothiocyanate (PEITC) and promotion of apoptosis in LNCaP cells

Pharmacological Role of Dietary Polyphenols in Prostate Cancer Chemoprevention

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