title: 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.
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Elinor
authors.initials: E
authors.lastname: Breiner-Goldstein
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Zoharia
authors.initials: Z
authors.lastname: Evron
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Frenkel
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Cohen
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Keren Nir
authors.initials: KN
authors.lastname: Meiron
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Peer
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Roichman
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Flescher
authors.affiliation: School of Chemistry, George S. Wise Faculty of Life Sciences, Department of Cell Research and Immunology, and School of Medicine, Clinical Microbiology and Immunology, Tel Aviv University , Tel Aviv 66978, Israel.
authors.forename: Micha
authors.initials: M
authors.lastname: Fridman
keywords: Anathracycline analogues; P-glycoproteins; aloe-emodin; anthranoids; antitumor agents