美國(guó)加利福尼亞的研究者發(fā)表了一些新的證據(jù)，可以解釋石榴汁對(duì)抗前列腺癌的神秘作用,。這項(xiàng)研究發(fā)表在9月19日美國(guó)化學(xué)學(xué)會(huì)期刊《農(nóng)業(yè)與食品化學(xué)》上，Navindra Seeram及其同事發(fā)現(xiàn)這種酸甜的時(shí)尚飲料還能搜尋并破壞前列腺癌細(xì)胞,。
據(jù)PhysOrg報(bào)道,，在之前的研究中，Seeram的研究小組發(fā)現(xiàn)飲用石榴汁有利于前列腺癌患者體內(nèi)PSA(一種前列腺抗原)水平升高,，而PSA水平升高是癌癥發(fā)展中“倍增時(shí)間”預(yù)告的關(guān)鍵指標(biāo),，PSA水平在短期內(nèi)倍增的人更傾向于死于癌癥。石榴汁能使“倍增時(shí)間”四倍增加,。
在這項(xiàng)新的研究中,，研究者在實(shí)驗(yàn)室實(shí)驗(yàn)中發(fā)現(xiàn)了一些證據(jù)，證明石榴的“搜尋和破壞”作用方式,。石榴汁中含有豐富的鞣花單寧（ET）抗氧化劑,，可代謝生成尿石素（urolithin）。研究者指出在給患有前列腺癌的小鼠口服或注射石榴汁后,，尿石素會(huì)在其前列腺組織內(nèi)高度集中,。他們還指出在細(xì)胞培養(yǎng)實(shí)驗(yàn)中尿石素能夠抑制人類前列腺癌細(xì)胞的生長(zhǎng)。
研究者表示,，石榴中鞣花單寧的化學(xué)預(yù)防潛力在小鼠前列腺組織的生物活性代謝物靶向,，意味著石榴在前列腺癌治療和化學(xué)預(yù)防中可能很有前途。他們建議再進(jìn)一步進(jìn)行相關(guān)的臨床實(shí)驗(yàn),。
原始出處:
J. Agric. Food Chem., 55 (19), 7732–7737 10.1021/jf071303g
Web Release Date: August 28, 2007 Copyright © 2007 American Chemical Society
Pomegranate Ellagitannin-Derived Metabolites Inhibit Prostate Cancer Growth and Localize to the Mouse Prostate Gland
Navindra P. Seeram,*† William J. Aronson,‡ Yanjun Zhang,† Susanne M. Henning,† Aune Moro,† Ru-po Lee,† Maryam Sartippour,† Diane M. Harris,† Matthew Rettig,§ Marc A. Suchard,∥ Allan J. Pantuck,‡ Arie Belldegrun,‡ and David Heber†
Center for Human Nutrition, Department of Urology, Department of Medicine at the Greater Los Angeles VA Medical Center, and Biomathematics and Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095
Received May 3, 2007
Abstract:
Our group has shown in a phase II clinical trial that pomegranate juice (PJ) increases prostate specific antigen (PSA) doubling time in prostate cancer (CaP) patients with a rising PSA. Ellagitannins (ETs) are the most abundant polyphenols present in PJ and contribute greatly towards its reported biological properties. On consumption, ETs hydrolyze to release ellagic acid (EA), which is then converted by gut microflora to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one (urolithin A, UA) derivatives. Despite the accumulating knowledge of ET metabolism in animals and humans, there is no available data on the pharmacokinetics and tissue disposition of urolithins. Using a standardized ET-enriched pomegranate extract (PE), we sought to further define the metabolism and tissue distribution of ET metabolites. PE and UA (synthesized in our laboratory) were administered to C57BL/6 wild-type male mice, and metabolite levels in plasma and tissues were determined over 24 h. ET metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues as compared to other tissues after administration of PE or UA. We also evaluated the effects of PE on CaP growth in severe combined immunodeficient (SCID) mice injected subcutaneously with human CaP cells (LAPC-4). PE significantly inhibited LAPC-4 xenograft growth in SCID mice as compared to vehicle control. Finally, EA and several synthesized urolithins were shown to inhibit the growth of human CaP cells in vitro. The chemopreventive potential of pomegranate ETs and localization of their bioactive metabolites in mouse prostate tissue suggest that pomegranate may play a role in CaP treatment and chemoprevention. This warrants future human tissue bioavailability studies and further clinical studies in men with CaP.
Figure 1. Chemical structures of the major pomegranate ET, punicalagin (occurs as a pair of anomers hence referred to as punicalagins), and its metabolites, EA and UA.
Keywords: Pomegranate; ellagitannins; urolithins; metabolite; tissue disposition; prostate cancer.
全文鏈接：http://pubs.acs.org/cgi-bin/sample.cgi/jafcau/2007/55/i19/html/jf071303g.html
