Original ContributionMechanisms of BSO (L-BUTHIONINE (cas 13073-21-7)-S,R-sulfoximine)-induced cytotoxic effects in neuroblastoma

Add time:09/28/2019    Source:sciencedirect.com

Glutathione (GSH) depletion is widely used to sensitize cells to anticancer treatment inducing the progression of programmed cell death and overcoming chemoresistance. It has been reported that neuroblastoma cells with MYCN amplification are unable to start TRAIL-dependent death and MYCN, in concert with cytotoxic drugs, efficiently induces the mitochondrial pathway of apoptosis through oxidative mechanisms. In this study, we show that GSH loss induced by L-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis, leads to overproduction of reactive oxygen species (ROS) and triggers apoptosis of MYCN-amplified neuroblastoma cells. BSO susceptibility of SK-N-BE-2C, a representative example of MYCN-amplified cells, has been attributed to stimulation of total SOD activity in the absence of changes in the level and the activity of catalase. Therefore, the unbalanced intracellular redox milieu has been demonstrated to be critical for the progression of neuroblastoma cell death that was efficiently prevented by antioxidants and rottlerin. These results describe a novel pathway of apoptosis dependent on ROS formation and PKC-delta activation and independent of p53, bcl-2, and bax levels; the selective redox modulation of PKC-delta might be suggested as a potential strategy for sensitizing MYCN-amplified cells to therapeutic approaches.

We also recommend Trading Suppliers and Manufacturers of L-BUTHIONINE (cas 13073-21-7). Pls Click Website Link as below: cas 13073-21-7 suppliers

Prev:Potential of L-BUTHIONINE (cas 13073-21-7) sulfoximine to enhance the apoptotic action of estradiol to reverse acquired antihormonal resistance in metastatic breast cancer☆
Next:Melanin content and downregulation of glutathione S-transferase contribute to the action of L-BUTHIONINE (cas 13073-21-7)-S-sulfoximine on human melanoma)