Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis

Naiki‐Ito, Aya; Chewonarin, Teera; Tang, Mingxi; Pitchakarn, Pornsiri; Kuno, Toshiki; Ogawa, Kumiko; Asamoto, Makoto; Shirai, Tomoyuki; Takahashi, Satoru

doi:10.1002/pros.22900

Cited by 60 publications

(48 citation statements)

References 27 publications

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“…18 In contrast, PJ and punicalagin were reported to suppress hypoxiainduced, cobalt chloride-induced, or staurosporine-induced apoptotic cell death in human placental trophoblasts. 19 Possible explanations for this discrepancy between the anti-apoptotic effects of PJ on placental trophoblasts versus its pro-apoptotic effects on macrophages shown herein could be related to the effects of PJ on different cells and to different stimuli used to induce cell death.…”

Section: A C C E P T E Dmentioning

confidence: 95%

“…17-19 PJ and its polyphenols were shown to possess anti-proliferative activity and to induce apoptosis in various human tumor cell lines. [17][18] Also, PJ and ellagic acid were recently reported to suppress prostate carcinogenesis via induction of apoptosis in the transgenic rat model for prostate adenocarcinoma. 18 On the other hand, in human placental trophoblasts, PJ and punicalagin were found to attenuate apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…[17][18] Also, PJ and ellagic acid were recently reported to suppress prostate carcinogenesis via induction of apoptosis in the transgenic rat model for prostate adenocarcinoma. 18 On the other hand, in human placental trophoblasts, PJ and punicalagin were found to attenuate apoptosis. 19 The effects of PJ on the mode of cell death of macrophages, the predominant cells during early atherosclerotic lesion development, are still not known.…”

Section: Introductionmentioning

confidence: 99%

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Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress

Rom

Volkova

Nandi

et al. 2016

Journal of Cardiovascular Pharmacology

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At high concentrations, polyphenols induce cell death, and the polyphenols-rich pomegranate juice (PJ), known for its antioxidative/antiatherogenic properties, can possibly affect cell death, including macrophage death involved in atherogenesis. In the present study, apoptotic/necrotic macrophage death was analyzed in J774A.1 macrophages and in peritoneal macrophages isolated from atherosclerotic apoE-/- mice treated with PJ. The effects of PJ were compared with those of the free radical generator 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Both PJ and AAPH significantly increased J774A.1 macrophage death; however, flow cytometric and microscopic analyses using annexin V/propidium iodide revealed that PJ increased the early apoptosis of the macrophage dose dependently (up to 2.5-fold, P < 0.01), whereas AAPH caused dose-dependent increases in late apoptosis/necrosis (up to 12-fold, P < 0.001). Unlike PJ, AAPH-induced macrophage death was associated with increased intracellular oxidative stress (up to 7-fold, P < 0.001) and with lipid stress demonstrated by triglyceride accumulation (up to 3-fold, P < 0.01) and greater chromatic vesicle response to culture medium (up to 5-fold, P < 0.001). Accordingly, recombinant paraoxonase 1, which hydrolyzes oxidized lipids, attenuated macrophage death induced by AAPH, but not by PJ. Similar apoptotic and oxidative effects were found in macrophages from apoE-/- mice treated with PJ or AAPH. As macrophage apoptotic/necrotic death has considerable impact on atherosclerosis progression, these findings may provide novel mechanisms for the antiatherogenicity of PJ.

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Section: A C C E P T E Dmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress

Rom

Volkova

Nandi

et al. 2016

Journal of Cardiovascular Pharmacology

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“…Ellagic acid (EA) is a dietary polyphenol that has been reported to show antioxidant, anti-adipogenic and cancer chemopreventive effects in a number of preclinical studies (Ding et al, 2014;Naiki-Ito et al, 2015;Okla et al, 2015). However, dietary free EA is a minor polyphenol and mainly occurs as a constituent of ellagitannins (ETs), or conjugates with different monosaccharides (EA-glycosides).…”

Section: Introductionmentioning

confidence: 99%

Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts

González‐Sarrías

Garcı́a-Villalba

Núñez‐Sánchez

et al. 2015

Journal of Functional Foods

134

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Available online A B S T R A C TEllagic acid (EA) is a polyphenol that must be released from the non-bioavailable ellagitannins in pomegranates, walnuts or strawberries to be absorbed. To estimate whether EA bioavailability could be improved after consumption of a high free EA amount, we conducted a crossover pharmacokinetic study in healthy volunteers that consumed two pomegranate extracts providing either 130 mg punicalagin+524 mg EA (PE-1) or 279 mg punicalagin+25 mg EA (PE-2).Targeted metabolomics (UPLC-ESI-qTOF-MS/MS) identified plasma free EA but not phase-II conjugates. EA pharmacokinetics showed high interindividual variability. Cmax ranged from 12 to 360 nM (PE-1: 74.8 ± 54.4 nM; PE-2: 64.1 ± 76.8 nM). In vitro digestion supported in vivo results. EA bioavailability was limited by the ellagitannin, pH and protein environment. A higher free EA intake does not enhance its bioavailability but promotes urolithin production. Bioavailability of EA, as the unchanged fraction that reaches the systemic circulation, is not as low as previously thought.

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“…Furthermore, both walnut extracts and ellagitannins have also been linked to suppressing prostate cancer cell proliferation and inducing apoptosis (Losso et al, 2004;Alshatwi et al, 2012;Vicinanza et al, 2013;Naiki-Ito et al, 2015) in several models. These cell-based assays allow for the identification of molecular pathways where walnut polyphenols may exert their activity.…”

Section: Prostatementioning

confidence: 99%

Health benefits of walnut polyphenols: An exploration beyond their lipid profile

Sánchez-González

Ciudad

Noé

et al. 2017

Critical Reviews in Food Science and Nutrition

106

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Walnuts are commonly found in our diet and have been recognized for their nutritious properties for a long time. Traditionally, walnuts have been known for their lipid profile which has been linked to a wide array of biological properties and health-promoting effects. In addition to essential fatty acids, walnuts contain a variety of other bioactive compounds such as, vitamin E and polyphenols. Among common foods and beverages, walnuts represent one of the most important sources of polyphenols, hence, their effect over human health warrants attention. The main polyphenol in walnuts is pedunculagin, an ellagitannin. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A and

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Ellagic acid, a component of pomegranate fruit juice, suppresses androgen-dependent prostate carcinogenesis via induction of apoptosis

Abstract: The results indicate that PFJ and EA are potential chemopreventive agents for prostate cancer, and EA may be the active component of PFJ that exerts these anti-cancer effects.

Cited by 60 publications

References 27 publications

Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress

Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress

Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts

Health benefits of walnut polyphenols: An exploration beyond their lipid profile

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