Reversible Increase in Resistance of A-431 Carcinoma Cells to TRAIL-Induced Apoptosis in Confluent Cultures Corresponds to a Decrease in Expression of DR4 and DR5 Receptors

-TRAIL (TNF alpha Related Apoptosis Inducing Ligand) cytokine is of great interest for the development of targeted antitumor drugs. We have previously found a reversible increase in tumour cell resistance to TRAIL-induced apoptosis in confluent cultures. In this work we show that increase in resistance of A-431 cells to TRAIL-induced death in confluent culture is associated with reduced expression of pro-apoptotic receptors DR4 and DR5 with absence of anti-apoptotic receptors DcR1 and DcR2 on cell surface. Decreased representation of DR4 and DR5 receptors on the cell surface is accompanied by a lack of activation of the pro-apoptotic protein Bid, effector caspase 3 under the action of recombinant protein izTRAIL, which leads to an increase in TRAIL resistance. Our results indicate that reversible increase in resistance of human carcinoma A-431 cells to TRAIL-induced apoptosis in confluent cultures is caused by decrease in expression of DR4 and DR5 receptors on cell surface.

Automated summary

In this study, we found that the increased resistance of A-431 cells to TRAIL-induced apoptosis in confluent cultures is associated with reduced expression of pro-apoptotic receptors DR4 and DR5, as well as the absence of anti-apoptotic receptors DcR1 and DcR2 on the cell surface. The decreased representation of DR4 and DR5 receptors is accompanied by a lack of activation of the pro-apoptotic protein Bid and effector caspase 3 under the action of recombinant protein izTRAIL, leading to an increase in TRAIL resistance. These results suggest that the reversible increase in TRAIL resistance in A-431 cells is caused by a decrease in the expression of DR4 and DR5 receptors on the cell surface.