In this study we report that the multidrug resistance protein (MRP) transports calcein from the cytoplasmic compartment of tumor cells, in contrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited by probenecid and vincristine. Intracellular glutathione (GSH) depletion which occurred when ce...

Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases; one such ailment is Alzheimer's disease. Using the Alzheimer's disease-associated amyloid beta protein, glutamate, hydrogen peroxide, and buthionine sulfoximine, we investigated the neuroprotective potential of estrogen against oxidative stress-induced cell death....

We investigated the effects of capillin, a constituent of Artemisia monosperma, on four human tumour cell lines: colon carcinoma H729, pancreatic carcinoma MIA PaCa-2, epidermoid carcinoma of the larynx HEp-2 and lung carcinoma A549. Cells were treated with capillin to examine both the anti-proliferative and pro-apoptotic effects, as well as the molecular mechanism underlying these effects. Cha...

Carotenoids are considered to act as antioxidants and protect humans from serious disorders such as skin degeneration and ageing, cardiovascular disease, certain types of cancer, and age-related diseases of the eye. In this study, these chemopreventive activities of a carotenoids-overexpressing transgenic carrot were evaluated. The results of DPPH, hydroxyl, and superoxide radical scavenging te...

Intravenous doses of buthionine sulfoximine (BSO, NSC 326231), an inhibitor of glutathione synthesis, were eliminated rapidly from mouse plasma in a biexponential manner. The initial phase of the plasma concentration versus time curve had a half-life of 4.9 min and accounted for 94% of the total area under the curve. The half-life of the terminal phase of the curve was 36.7 min and the area acc...

Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically e...

Glutathione (GSH) plays a crucial role in the protection of normal and tumor tissue against the toxic effects of numerous chemotherapeutic drugs. Therefore, the possible therapeutic benefit of thiol depletion in cancer treatment is dependent upon the relative degree to which tumor or normal tissue is sensitized to the toxic effects of subsequent chemotherapy. To address this issue, the followin...

Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered ...

Glutathione plays a central role in maintaining cellular redox homeostasis, and modulations to this status may affect malaria parasite sensitivity to certain types of antimalarials. In this study, we demonstrate that inhibition of glutathione biosynthesis in the Plasmodium berghei ANKA strain through disruption of the γ-glutamylcysteine synthetase (γ-GCS) gene, which encodes the first and rate-...