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Targeting anthracycline-resistant tumor cells with synthetic aloe-emodin glycosides.

ABSTRACT: The cytotoxic activity of aloe-emodin (AE), a natural anthranoid that readily permeates anthracycline-resistant tumor cells, was improved by the attachment of an amino-sugar unit to its anthraquinone core. The new class of AE glycosides (AEGs) showed a significant improvement in cytotoxicity-up to more than 2 orders of magnitude greater than those of AE and the clinically used anthracycline doxorubicin (DOX)-against several cancer cell lines with different levels of DOX resistance. Incubation with the synthetic AEGs induced cell death in less than one cell cycle, indicating that these compounds do not directly target the cell division mechanism. Confocal microscopy provided evidence that unlike DOX, AEGs accumulated in anthracycline-resistant tumor cells in which resistance is conferred by P-glycoprotein efflux pumps. The results of this study demonstrate that AEGs may serve as a promising scaffold for the development of cytotoxic agents capable of overcoming anthracycline resistance in tumor cells.

SUBMITTER: Breiner-Goldstein E

PROVIDER: S-EPMC4018067 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Targeting anthracycline-resistant tumor cells with synthetic aloe-emodin glycosides.

Breiner-Goldstein Elinor E Evron Zoharia Z Frenkel Michael M Cohen Keren K Meiron Keren Nir KN Peer Dan D Roichman Yael Y Flescher Eliezer E Fridman Micha M

ACS medicinal chemistry letters 20110512 7

The cytotoxic activity of aloe-emodin (AE), a natural anthranoid that readily permeates anthracycline-resistant tumor cells, was improved by the attachment of an amino-sugar unit to its anthraquinone core. The new class of AE glycosides (AEGs) showed a significant improvement in cytotoxicity-up to more than 2 orders of magnitude greater than those of AE and the clinically used anthracycline doxorubicin (DOX)-against several cancer cell lines with different levels of DOX resistance. Incubation wi ...[more]

PMID: 24900344

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Project description:Aloe arborescens is a relevant species largely used in traditional medicine of several countries. In particular, the decoction of leaves is prepared for various medicinal purposes including antidiabetic care. The aim of this research was the study of the antiglycation activity of two A. arborescens leaf extracts and isolated compounds: aloin and aloe-emodin. These phytoconstituents were quantitatively assessed in methanolic and hydroalcoholic extracts using high performance liquid chromatography (HPLC) analysis. In addition, the total phenolic and flavonoid contents were detected. In order to study their potential use in diabetic conditions, the antiglycation and antiradical properties of the two extracts and aloin and aloe-emodin were investigated by means of bovine serum albumin (BSA) and 1,1-diphenyl-2-picryl-hydrazil (DPPH) assays; further, their cytotoxicity in HT-29 human colon adenocarcinoma cells was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, the ability of aloin and aloe-emodin to permeate the cellular membranes of HT-29 cells was determined in order to estimate their potential in vivo absorption. This assessment indicated that aloe-emodin can substantially pass through cell membranes (~20%), whereas aloin did not permeate into HT-29 cells. Overall, the data show that both the methanolic and the hydroalcoholic A. arborescens extracts determine significant inhibition of glycation and free-radical persistence, without any cytotoxic activity. The data also show that the antiglycation and the antiradical activities of aloin and aloe-emodin are lower than those of the two extracts. In relation to the permeability study, only aloe-emodin is able to cross HT-29 cellular membranes, showing the attitude to pass through the intestinal layer. Overall, the present data surely support the traditional use of A. arborescens leaf extracts against hyperglycemic conditions, while aloin and aloe-emodin as potential drugs need further study.

Dataset Information

Targeting anthracycline-resistant tumor cells with synthetic aloe-emodin glycosides.

Publications

Targeting anthracycline-resistant tumor cells with synthetic aloe-emodin glycosides.

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