Kinetic studies of the effects of Temodal and quercetin on astrocytoma cells.
Journal Title: Pharmacological Reports - Year 2011, Vol 63, Issue 2
Abstract
The aim of the present study was to investigate the kinetics of the effects exerted by Temodal and quercetin on the survival of the human astrocytoma MOGGCCM cell line. Our results indicate that quercetin was toxic and induced necrosis, whereas Temodal induced autophagy-mediated cell death most effectively. The amount of cell death directly correlated with drug concentration and length of exposure. During combined administration of both drugs, Temodal attenuated the cytotoxic effects of quercetin. Combinations of both drugs were effective in inducing programmed cell death, but the type of cell death was concentration-dependent. Co-administration of Temodal (100 μM) with a low quercetin concentration (5 μM) resulted in a very significant induction of autophagy; however, after treatment with quercetin at a higher concentration (30 μM), apoptosis became the primary mechanism of cell death. The sequence of drug administration was also important. The highest number of dead cells was observed after simultaneous administration of both drugs or after pre-incubation with Temodal followed by treatment with quercetin. Apoptosis was identified through activation of the mitochondrial pathway including cleavage of caspase-3 and release of cytochrome c. Autophagy was identified through increased levels of LC3II. Our results indicate that Temodal and quercetin are synergistic inducers of programmed cell death, better together than applied separately. This drug combination appears to be a potent and promising therapeutic relevant to the treatment of gliomas.
Authors and Affiliations
Joanna Jakubowicz-Gil, Ewa Langner, Wojciech Rzeski
Keywords
Related Articles
- EP ID EP145157
- DOI -
- Views 80
- Downloads 0
Microarray analysis of altered gene expression in diallyl trisulfide-treated HepG2 cells.
Diallyl trisulfide (DT) is a natural compound derived from garlic. Despite its reported lipid-lowering effects, the mechanisms of its actions are not clear yet. To further understand the molecular mechanisms of actions o...
Evaluation of the antioxidative properties of lipoxygenase inhibitors.
Background: Oxidative stress is a component of many pathological conditions including neurodegenerative diseases and inflammation. An important source of reactive oxygen species (ROS) are lipoxygenases (LOX) - enzymes re...
Effect of indometacin pretreatment on protamine sulfate-mediated relaxation of the isolated rat uterus: the role of the antioxidative defense system.
Previous results in this laboratory indicate that protamine sulfate (PS) evokes dose-dependent relaxation of both spontaneous and calcium ion-induced uterus activity mediated predominantly by potassium channels and, to a...
Study of the interaction of glutamatergic and nitrergic signalling in conditions of the experimental airways hyperreactivity.
Background: Glutamatergic and nitrergic system participate in the control of respiratory system functions. It is only little information regarding a possible interaction of both systems in the airways hyperractivity. We...
Modulatory role of 5-HT(1B) receptors in the discriminative signal of amphetamine in the conditioned taste aversion paradigm.
Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely mediated by increased DA neurotransmission in the nucleus accumben...