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

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Abstract

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.

About the authors

R. S. Fadeev

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences; Puschino State Natural Science Institute

Author for correspondence.
Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino; Russia, 142290, Moscow oblast, Pushchino

N. V. Dolgikh

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino

A. V. Chekanov

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino

A. S. Senotov

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino

K. S. Krasnov

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences; Puschino State Natural Science Institute

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino; Russia, 142290, Moscow oblast, Pushchino

M. I. Kobyakova

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino

Ya. V. Lomovskaya

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino

I. S. Fadeevа

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences; Puschino State Natural Science Institute

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino; Russia, 142290, Moscow oblast, Pushchino

V. S. Akatov

Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences; Puschino State Natural Science Institute

Email: fadeevrs@gmail.com
Russia, 142290, Moscow oblast, Pushchino; Russia, 142290, Moscow oblast, Pushchino

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Copyright (c) 2023 Р.С. Фадеев, Н.В. Долгих, А.В. Чеканов, А.С. Сенотов, К.С. Краснов, М.И. Кобякова, Я.В. Ломовская, И.С. Фадеева, В.С. Акатов

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