TY - JOUR
T1 - Monitoring drug induced apoptosis and treatment sensitivity in non-small cell lung carcinoma using dielectrophoresis
AU - Taruvai Kalyana Kumar, Rajeshwari
AU - Liu, Shanshan
AU - Minna, John D.
AU - Prasad, Shalini
N1 - Funding Information:
This work was funded by Cecil and Ida Green Endowment in Systems Biology at University of Texas at Dallas and grant funded by Lung Cancer SPORE P50CA70907 . We thank Dr. Nesreen Al-smadi and Christopher Lewis from Schmidtke Laboratory at UT Dallas for their valuable inputs in flow cytometry data collection and analysis. We also thank Dr. Bryan Black from Neuronal Networks and Interfaces Laboratory at UT Dallas for his help with confocal microscope image acquisition and analysis.
Publisher Copyright:
© 2016 Published by Elsevier B.V.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2 h post drug treatment as compared to 24 h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24 h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events.
AB - Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2 h post drug treatment as compared to 24 h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24 h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events.
KW - Apoptosis monitoring
KW - Dielectrophoresis
KW - Non invasive electrokinetics
KW - Non-small cell lung cancer
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U2 - 10.1016/j.bbagen.2016.05.039
DO - 10.1016/j.bbagen.2016.05.039
M3 - Article
C2 - 27262539
AN - SCOPUS:84974539363
SN - 0304-4165
VL - 1860
SP - 1877
EP - 1883
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 9
ER -