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Compound-mediated Cytotoxicity

Kinetic Response Profi les Refl ect Different Cytotoxic Mechanisms


HepG2 cells were treated with various cytotoxic compounds and monitored in real time for cytotoxic response kinetics. Representative compounds targeting tubulin (paclitaxel), actin (cytochalasin D), DNA (doxorubicin), mitochondria (rotenone), calcium homeostasis (thapsigargin), and protein transport (brefeldin A) generated distinct response profiles. (Data and figure adapated from ACEA Biosciences, Inc. unpublished data).  

 

Real Time Monitoring Allows Identifi cation of Optimal Timepoints for Further Analysis​

HeLa cells were treated with cytotoxic compounds and monitored in real time for cytotoxic response kinetics on xCELLigence. At the indicated timepoints, cells in a parallel plate were analyzed using the WST-1 cell viability assay. 5-FU or MG132 caused different dose-dependant kinetic response profiles with different optimal times for performing the WST-1 assay. (Data and figure adapted from from Ke N, et. al., 2011).

SELECT Publications for Drug-Mediated Cytotoxicity/Apoptosis 

1.The xCELLigence system for real-time and label-free monitoring of cell viability. 
Ke N, Wang X, Xu X, Abassi Y. 
Methods Mol Biol. 2011;740:33-43. 

2.Kinetic cell-based morphological screening: prediction of mechanism of compound action  and off-target effects.  
Abassi YA, Xi B, Zhang W, Ye P, Kirstein SL, Gaylord MR, Feinstein SC, Wang X, Xu X. (2009).  
Chem Biol. 2009;16:712-23. 

3.Dynamic monitoring of cytotoxicity on microelectronic sensors.  
Xing JZ, Zhu L, Jackson JA, Gabos S, Sun XJ, Wang XB, Xu X.  
Chem Res Toxicol. 2005;18:154-61. 

Key Benefits 

• Kinetic responses can be predictive of mechanism of action. 
• Continuous monitoring ensures no meaningful time points are missed. 
• Real-time data allows identification of the optimal times for treatment and data collection. 
• Non-invasive assay is performed in tissue culture incubator, allowing for analysis by standard viability assays at any point during the experiment. 
• Easy quantification of the onset and kinetics of the cytotoxic response.