Identification of Xanthones as Selective Killers of Cancer Cells Overexpressing the ABC Transporter MRP1

• DOI: 10.1002/cmdc.201100102
• Publication Date: 2011-06-01T13:27:47Z
• Authors: Estelle Genoux‐Ba...; Doriane Lorendeau; Edwige Nicolle; Samir Yahiaoui; Sandrine Magnard; Attilio Di Pietro; Hélène Baubichon‐...; Ahcène Boumendjel
• Keywords: Identification

Abstract Multidrug‐resistance protein 1 (MRP1) belongs to the ATP‐binding cassette (ABC) transporter family. MRP1 mediates MDR (multidrug resistance) by causing drug efflux either conjugation glutathione (GSH) or co‐transport with free GSH (without covalent bonding between and GSH). We recently reported that calcium channel blocker verapamil can activate massive in MRP1‐overexpressing cells, leading cell death through apoptosis. However, clinical use of is hampered its cardiotoxicity. Then, search for compounds act similarly verapamil, but without major side effects, we investigated xanthones. Herein show xanthones induce apoptosis among resistant cells overexpressing effect. Among studied, 1,3‐dihydroxy‐6‐methoxyxanthone was identified as most active derivative, able specifically kill transfected human even greater potency than verapamil. Under same conditions, have no toxic effect on control (sensitive) cells. Xanthones could therefore be considered new potential anticancer agents selective treatment MRP1‐positive tumors.