Dataset Information

Conjugation of 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo.

ABSTRACT: The carbohydrate moieties on conjugating with 3-(1'-hexyloxyethyl)-3-devinyl pyropeophorbide-a (HPPH) altered the uptake and intracellular localization from mitochondria to lysosomes. In vitro, HPPH-Gal 9 PDT showed increased PDT efficacy over HPPH-PDT as detectable by the oxidative cross-linking of nonphosphorylated STAT3 and cell killing in ABCG2-expressing RIF cells but not in ABCG2-negative Colon26 cells. This increased efficacy in RIF cells could at least partially be attributed to increased cellular accumulation of 9, suggesting a role of the ABCG2 transporter for which HPPH is a substrate. While such differences in the accumulation in HPPH derivatives by tumor tissue in vivo were not detectable, 9 still showed an elevated light dose-dependent activity compared to HPPH in mice bearing RIF as well as Colon26 tumors. Further optimization of the carbohydrate conjugates at variable treatment parameters in vivo is currently underway.

SUBMITTER: Zheng X

PROVIDER: S-EPMC2913405 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Conjugation of 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo.

Zheng Xiang X Morgan Janet J Pandey Suresh K SK Chen Yihui Y Tracy Erin E Baumann Heinz H Missert Joseph R JR Batt Carrie C Jackson Jennifer J Bellnier David A DA Henderson Barbara W BW Pandey Ravindra K RK

Journal of medicinal chemistry 20090701 14

The carbohydrate moieties on conjugating with 3-(1'-hexyloxyethyl)-3-devinyl pyropeophorbide-a (HPPH) altered the uptake and intracellular localization from mitochondria to lysosomes. In vitro, HPPH-Gal 9 PDT showed increased PDT efficacy over HPPH-PDT as detectable by the oxidative cross-linking of nonphosphorylated STAT3 and cell killing in ABCG2-expressing RIF cells but not in ABCG2-negative Colon26 cells. This increased efficacy in RIF cells could at least partially be attributed to increase ...[more]

PMID: 19507863

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Project description:The subcellular distribution of Mg2+-dependent phosphatidate phosphohydrolase in rat adipocytes between a soluble and a membrane-bound fraction was measured by using both centrifugal fractionation and a novel Millipore-filtration method. The relative proportion of the phosphohydrolase associated with the particulate fraction was increased on incubation of cells with noradrenaline or palmitate. Insulin on its own decreased the proportion of the phosphohydrolase that was particulate and abolished the effect of noradrenaline, but not that of palmitate. The effect of noradrenaline on phosphohydrolase distribution was rapid, the effect being maximal within 10 min. Noradrenaline exerted this effect with a similar concentration-dependence to its lipolytic effect. Inclusion of albumin in homogenization buffers decreased the proportion of the phosphohydrolase that was particulate, but did not abolish the effect of noradrenaline. There was limited correlation between the proportion of the phosphohydrolase that was particulate and the measured rate of triacylglycerol synthesis in adipocytes incubated under a variety of conditions. Starvation, streptozotocin-diabetes and hypothyroidism decreased the specific activities of the phosphohydrolase and glycerolphosphate acyltransferase in homogenates from epididymal fat-pads. Restoration of these activities in the diabetic state was seen after administration of insulin over 2 days or, in the short term, within 2 h after a single administration of insulin. Administration of thyroxine over 3 days caused restoration of these activities in the hypothyroid state. Starvation and diabetes increased the proportion of the phosphohydrolase found in the microsomal fraction. This change was not seen when albumin was present in homogenization buffers. The possible role of fatty acids as regulators of the intracellular translocation of the phosphohydrolase, together with the role of this enzyme in the regulation of triacylglycerol synthesis in adipose tissue, is discussed.

Dataset Information

Conjugation of 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo.

Publications

Conjugation of 2-(1'-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH) to carbohydrates changes its subcellular distribution and enhances photodynamic activity in vivo.

Similar Datasets

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