title: 2,2'-Dihydroxychalcone, a glutathione transferase inhibitor, sensitises human colon adenocarcinoma cells to chlorambucil and melphalan, but not to actinomycin D.
abstract: 2,2'-Dihydroxychalcone (2,2'DHC) is a potent inhibitor of glutathione S-transferases (GSTs). Pre-treatment of human colon cancer cells by a non-toxic concentration of this GST inhibitor significantly sensitised cancer cells to chlorambucil and melphalan, which are substrates of glutathione (GSH) conjugation. However, sensitisation to actinomycin D, which has not been shown to be detoxified by GSH-related mechanisms, was not observed. These results further confirm the contribution of GSH-related mechanisms to drug resistance by increased detoxification of drugs. 2,2'DHC inhibited GST activity and the transport of GSH conjugates by cancer cells. Its combined effects on GST and glutathione conjugate export (GS-X) pump may provide more potent sensitisation of cancer cells to chemotherapeutic drugs.
authors.affiliation: Department of Experimental Surgery, Singapore General Hospital, Singapore 169608.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Goh
authors.forename: Yufan
authors.initials: Y
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Laichun
authors.initials: L
authors.lastname: Ong
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Pierce
authors.initials: P
authors.lastname: Chow
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang