The Interaction of the Flavonoid Fisetin with Human Glutathione Transferase A1-1

Glutathione transferases (GSTs) are a family of Phase II detoxification enzymes that are involved in the development of the multidrug resistance (MDR) mechanism in cancer cells and therefore affect the clinical outcome of cancer chemotherapy. The discovery of nontoxic natural compounds as inhibitors for GSTs is a promising approach for chemosensitizing and reversing MDR. Fisetin (7,3′,4′-flavon-3-ol) is a plant flavonol present in many plants and fruits. In the present work, the interaction of fisetin with human glutathione transferase A1-1 (hGSTA1-1) was investigated. Kinetic analysis revealed that fisetin is a reversible inhibitor for hGSTA1-1 with IC50 1.2 ± 0.1 μΜ. It functions as a mixed-type inhibitor toward glutathione (GSH) and as a noncompetitive inhibitor toward the electrophile substrate 1-chloro-2,4-dinitrobenzene (CDNB). In silico molecular modeling and docking predicted that fisetin binds at a distinct location, in the solvent channel of the enzyme, and occupies the entrance of the substrate-binding sites. Treatment of proliferating human epithelial colorectal adenocarcinoma cells (CaCo-2) with fisetin causes a reduction in the expression of hGSTA1-1 at the mRNA and protein levels. In addition, fisetin inhibits GST activity in CaCo-2 cell crude extract with an IC50 (2.5 ± 0.1 μΜ), comparable to that measured using purified recombinant hGSTA1-1. These actions of fisetin can provide a synergistic role toward the suppression and chemosensitization of cancer cells. The results of the present study provide insights into the development of safe and effective GST-targeted cancer chemosensitizers.

Isolation and Characterization of An Endosulfan-Degrading Strain, Stenotrophomonas sp. LD-6, and its Potential in Soil Bioremediation

Aerobic bacteria degrading endosulfan were isolated from contaminated sludge. One of the isolates, LD-6, was identified as Stenotrophomonas sp. The bacterium could utilize endosulfan as the sole source of carbon and sulfur. 100 mg/l endosulfan was completely degraded within 10 days, and endosulfan diol and endosulfan ether were detected as major metabolites with a slight decrease in culture pH. The results indicated that Stenotrophomonas. sp. LD-6 might degrade endosulfan by a non-oxidative pathway. Biodegradation of both isomers was relatively better at a temperature range of 25-35 degrees C, with a maximum at 30 degrees C. In addition, cell crude extract of strain LD-6 could metabolize endosulfan rapidly, and degradative enzymes were intracellular distributed and constitutively expressed. Besides, application of the strain was found to promote the removal of endosulfan in soil. This study might help with the future research in better understanding of the biodegradation.