Granaatappel(sap) en prostaatkanker.*
Uit eerdere studies is al gebleken dat granaatappel(sap) een verhoging van het PSA bij mannen met prostaatkanker sterk kan vertragen. Dit is een indicatie dat de kankercellen langzamer groeien. Dezelfde onderzoekers hebben in deze studie, weliswaar met muizen gekeken of dat inderdaad zo is. De speciaal behandelde muizen die extra granaatappelextracten kregen bleken duidelijk minder tumorgroei te hebben dan de muizen die deze extracten niet kregen. Het zijn vooral de bioactieve stoffen ellagitaninnes en derivaten zoals punicalagines die hiervoor verantwoordelijk zijn.
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
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. (Januari
2008)
Reacties:
