Stiffness changes of tumor HEp2 cells correlates with the inhibition and release of TRAIL-induced apoptosis pathways

• Published in: Journal of molecular recognition 2012-05, Vol.25 (5), p.299-308
• Main Authors: Targosz-Korecka, Marta, Biedron, Rafal, Szczygiel, Agnieszka Maria, Brzezinka, Grzegorz, Szczerbinski, Jacek, Zuk, Anna
• Format: Article
• Language: English
• Subjects: actinomycin D; Actins - metabolism; Antibiotics, Antineoplastic - pharmacology; Apoptosis; atomic force microscopy; Bcl-2; cell stiffness; Dactinomycin - pharmacology; Drug Therapy, Combination; Elasticity; Fluorescence; Humans; Laryngeal Neoplasms - drug therapy; Laryngeal Neoplasms - metabolism; Laryngeal Neoplasms - pathology; Microscopy, Atomic Force; nanoindentation spectroscopy; Rho; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL; Tumor Cells, Cultured
• ISSN: 0952-3499; 1099-1352
• DOI: 10.1002/jmr.2192

Tumor necrosis factor (TNF)‐related apoptosis inducing ligand (TRAIL) is a promising apoptotic agent that can selectively act on tumor cells. However, some cancer cells are resistant to TRAIL mediated apoptosis. In specific type of cells, sensitization by chemotherapeutic drugs may overcome the resistance to TRAIL induced apoptosis. In this work, atomic force microscopy (AFM) nanoindentation spectroscopy combined with fluorescence methods were used to investigate the biomechanical aspects of the resistance and unblocking of apoptosis in larynx carcinoma HEp2 cells treated with TRAIL. It is shown that there is a direct correlation between the increase in mechanical cell stiffness and the inhibition of apoptosis induced by TRAIL in HEp2 cells. Conversely, unblocking of apoptosis by sensitization of HEp2 cells with a chemotherapeutic drug Actinomycin D is related to the depolymerization of F‐actin and to the decrease in the cell stiffness. Both effects, that is, changes in the mechanical stiffness of the cell and the inhibition of apoptotic pathway, are closely related to the Bcl‐2 activity. Most probably, the depolymerization of F‐actin results from downregulation of Rho protein, which in turn is accompanied by a lower activity of Bcl‐2 and in consequence releases the intrinsic apoptotic channel. The presented results reveal a promising application of nanoindentation spectroscopy with an AFM tip as a novel tool for monitoring the processes of apoptosis inhibition. Copyright © 2012 John Wiley & Sons, Ltd.