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Prevention Research

Abstract 2871: Pharmacokinetics studies of anticancer gallotannin penta-O-galloyl-beta-D-glucose (PGG) in mice

Li Li, Jinhui Zhang, Ahamd Shaik, Katai Nhkata, Chengguo Xing and Junxuan Lü
Li Li
1Hormel Institute, University of Minnesota, Austin, MN
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Jinhui Zhang
1Hormel Institute, University of Minnesota, Austin, MN
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Ahamd Shaik
1Hormel Institute, University of Minnesota, Austin, MN
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Katai Nhkata
1Hormel Institute, University of Minnesota, Austin, MN
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Chengguo Xing
2Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN.
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Junxuan Lü
1Hormel Institute, University of Minnesota, Austin, MN
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DOI: 10.1158/1538-7445.AM10-2871 Published April 2010
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Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC

Abstract

Studies by our group and others have shown that 1, 2, 3, 4, 6-penta-O-galloyl-beta-D-glucose (PGG) exhibits in vivo anti-cancer effects against prostate and breast cancer xenograft or lung cancer allograft when administrated by i.p injection or oral gavage. PGG has also been shown in several studies to exhibit anti-diabetic activities both in vitro and in vivo. However, no data have been published on the absorption, distribution, metabolism and elimination (ADME) to provide mechanistic correlates to account for the biological activities. In this study, we developed a method for the analysis of PGG in mouse plasma, using tea polyphenol epigallocatechin gallate (EGCG) as an internal standard (IS). A liquid-liquid extraction (LLE) protocol originally developed for tea polyphenol analyses was optimized for the extraction of PGG from mouse plasma. In brief, plasma (0.2 ml) was acidified with an equal volume of 2% acetic acid, and ethyl acetate was then applied to extract PGG and EGCG (IS). After LLE, PGG was quantitated by HPLC with a UV detection at 280 nm. The method was validated according to FDA guidelines. The extraction efficiency for spiked PGG was ∼70 % in mouse plasma. The limit of detection (LOD) for PGG was approximately 100 ng/ml and the limit of quantitation (LOQ) around 200 ng/ml when using 200 µl mouse plasma. The linear range of the method was 0.2 −25 µg/ml in mouse plasma.

Pharmacokinetics of PGG following a single i.p. injection in mice was studied. The peak plasma PGG concentrations (Cmax) were found to be approximately 4 and 11 µM at administered dose of 20 and 80 mg/kg of PGG, respectively. The apparent half life of the elimination phase for PGG is 3 h. Addition of glucuronidase and sulfatase to plasma did not change extractable PGG. These data suggest that PGG exists in plasma mostly as free extractable form after a single i.p. injection and that the plasma resident time for PGG is several hours.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2871.

  • ©2010 American Association for Cancer Research
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Cancer Research: 70 (8 Supplement)
April 2010
Volume 70, Issue 8 Supplement
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Abstract 2871: Pharmacokinetics studies of anticancer gallotannin penta-O-galloyl-beta-D-glucose (PGG) in mice
Li Li, Jinhui Zhang, Ahamd Shaik, Katai Nhkata, Chengguo Xing and Junxuan Lü
Cancer Res April 15 2010 (70) (8 Supplement) 2871; DOI: 10.1158/1538-7445.AM10-2871

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Abstract 2871: Pharmacokinetics studies of anticancer gallotannin penta-O-galloyl-beta-D-glucose (PGG) in mice
Li Li, Jinhui Zhang, Ahamd Shaik, Katai Nhkata, Chengguo Xing and Junxuan Lü
Cancer Res April 15 2010 (70) (8 Supplement) 2871; DOI: 10.1158/1538-7445.AM10-2871
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Cancer Research Online ISSN: 1538-7445
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