美国加利福尼亚的研究者发表了一些新的证据,可以解释石榴汁对抗前列腺癌的神秘作用。这项研究发表在9月19日美国化学学会期刊《农业与食品化学》上,Navindra Seeram及其同事发现这种酸甜的时尚饮料还能搜寻并破坏前列腺癌细胞。
据PhysOrg报道,在之前的研究中,Seeram的研究小组发现饮用石榴汁有利于前列腺癌患者体内PSA(一种前列腺抗原)水平升高,而PSA水平升高是癌症发展中“倍增时间”预告的关键指标,PSA水平在短期内倍增的人更倾向于死于癌症。石榴汁能使“倍增时间”四倍增加。
在这项新的研究中,研究者在实验室实验中发现了一些证据,证明石榴的“搜寻和破坏”作用方式。石榴汁中含有丰富的鞣花单宁(ET)抗氧化剂,可代谢生成尿石素(urolithin)。研究者指出在给患有前列腺癌的小鼠口服或注射石榴汁后,尿石素会在其前列腺组织内高度集中。他们还指出在细胞培养实验中尿石素能够抑制人类前列腺癌细胞的生长。
研究者表示,石榴中鞣花单宁的化学预防潜力在小鼠前列腺组织的生物活性代谢物靶向,意味着石榴在前列腺癌治疗和化学预防中可能很有前途。他们建议再进一步进行相关的临床实验。
原始出处:
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.
全文链接:http://pubs.acs.org/cgi-bin/sample.cgi/jafcau/2007/55/i19/html/jf071303g.html