title: Inhibition of glutathione S-transferases by thonningianin A, isolated from the African medicinal herb, Thonningia sanguinea, in vitro.
abstract: There is evidence that increased expression of glutathione S-transferase (EC: 2.5.1.18, GST) is involved in resistance of tumor cells against chemotherapeutic agents. In this study we investigated the inhibitory effects of thonningianin A (Th A), a novel antioxidant isolated from the medicinal herb, Thonningia sanguinea on uncharacterized rat liver GST and human GST P1-1. Using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate, rat liver cytosolic GST activity was inhibited by Th A in a concentration dependent manner with 50% inhibition concentration (IC50) of 1.1 microM. When Th A was compared with known potent GST inhibitors the order of inhibition was tannic acid>cibacron blue>hematin>Th A>ethacrynic acid with CDNB as substrate. Th A also exhibited non-competitive inhibition towards both CDNB and glutathione. Furthermore, using 1,2-dichloro-4-nitrobenzene, ethacrynic acid and 1,2-epoxy-3-(p-nitrophenoxy) propane as substrates Th A at 1.0 microM inhibited cytosolic GST by 2%, 12% and 36% respectively. Human GST P1-1 was also inhibited by Th A with an IC50 of 3.6 microM. While Th A showed competitive inhibition towards CDNB it exhibited non-competitive inhibition towards GSH of the human GST P1-1. These results suggest that Th A represents a new potent GST in vitro inhibitor.
authors.affiliation: Laboratory of Molecular Pharmacology, Graduate School of Medicine, Okinawa 903-0215, Japan.
authors.forename: Maxwell Afari
authors.initials: MA
authors.lastname: Gyamfi
authors.forename: Ikuko Ichiba
authors.initials: II
authors.lastname: Ohtani
authors.forename: Etsuki
authors.initials: E
authors.lastname: Shinno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aniya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D031111:Balanophoraceae / Q000737:chemistry*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D047348:Hydrolyzable Tannins; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D016488:Medicine, African Traditional; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013634:Tannins / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D013634:Tannins; C411320:thonningianin A; D005982:Glutathione Transferase