22 research outputs found
Synergistic Anticancer Effects of the 9.2.27PE Immunotoxin and ABT-737 in Melanoma
In cancer, combinations of drugs targeting different cellular functions is well accepted to improve tumor control. We studied the effects of a Pseudomonas exotoxin A (PE) - based immunotoxin, the 9.2.27PE, and the BH-3 mimetic compound ABT-737 in a panel of melanoma cell lines. The drug combination resulted in synergistic cytotoxicity, and the cell death observed was associated with apoptosis, as activation of caspase-3, inactivation of Poly (ADP-ribose) polymerase (PARP) and increased DNA fragmentation could be prevented by pre-treatment with caspase and cathepsin inhibitors. We further show that ABT-737 caused endoplasmic reticulum (ER) stress with increased GRP78 and phosphorylated eIF2α protein levels. Moreover, treatment with ABT-737 increased the intracellular calcium levels, an effect which was enhanced by 9.2.27PE, which as a single entity drug had minimal effect on calcium release from the ER. In addition, silencing of Mcl-1 by short hairpin RNA (shRNA) enhanced the intracellular calcium levels and cytotoxicity caused by ABT-737. Notably, the combination of 9.2.27PE and ABT-737 caused growth delay in a human melanoma xenograft mice model, supporting further investigations of this particular drug combination
The effects of a competitive antagonist on GABA-evoked currents in the presence of sedative-hypnotic agents
Effects of Chronic Ethanol Consumption and Withdrawal on the Neuroactive Steroid 3α-Hydroxy-5α-pregnan-20-one in Male and Female Rats
Allelic Variation in the GABAA Receptor gamma2 Subunit Is Associated With Genetic Susceptibility to Ethanol-Induced Motor Incoordination and Hypothermia, Conditioned Taste Aversion, and Withdrawal in BXD/Ty Recombinant Inbred Mice
ADT-OH, a hydrogen sulfide-releasing donor, induces apoptosis and inhibits the development of melanoma in vivo by upregulating FADD
Diazepam-bound structure of the GABAA receptor identifies novel ligands for the benzodiazepine binding site
Benzodiazepines exert their anxiolytic, anticonvulsant, muscle-relaxant and sedative-hypnotic properties by allosterically enhancing the action of GABA at GAB