Oxidative stress induces cortical stiffening and cytoskeletal remodelling in pre-apoptotic cancer cells

Authors:

Aiman Jalmukhambetova1, Aidana Baltabekova1, Aizhan Tolebay1, Nargiz Rakhimgerey1, Ferdinand Molnár1, Tri Thanh Pham1, Agata N. Burska2,3 and Dos D. Sarbassov1,3
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Affiliations:

1 Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan. 2 Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan. 3 National Laboratory Astana, Center for Life Sciences, Nazarbayev University, Astana, Kazakhstan.

Keywords: 

oxidative stress, cortical stiffness, atomic force microscopy, F-actin, arsenic trioxide and D form of vitamin C, cancer migration.

Corresponding Author(s):

Agata N Burska, School of Medicine, Nazarbayev University, 5/1 Kerey and Zhanibek Khans Street, NU Medicine building office 322, Astana, 010000, Kazakhstan; Of-fice phone: +7 7172 69 6469; agata.burska@nu.edu.kz Dos D Sarbassov, Biology Department, School of Sciences and Humanities, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana, 010000 Kazakhstan; Office phone: +7 (7172) 70-58-73; dos.sarbassov@nu.edu.kz

Conflict of interest statement:

The authors declare no competing interests.

Please cite this article as:

Aiman Jalmukhambetova, Aidana Baltabekova, Aizhan Tolebay, Nargiz Rakhimgerey, Ferdinand Molnár, Tri Thanh Pham, Agata N. Burska and Dos D. Sarbassov (2025). Oxidative stress induces cortical stiffening and cytoskeletal remodelling in pre-apoptotic cancer cells. Cell Stress 9: 182-193. doi: 10.15698/cst2025.08.310

© 2025 Jalmukhambetova et al. This is an open-access article released under the terms of the Creative Commons Attrib-ution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

An imbalanced production of reactive oxygen species (ROS) is linked to various aspects of cancer development, including cytoskeletal remodelling. However, the relationship between ROS, actin and cellular stiffness remains controversial. Here, we show that oxidative stress increases cortical stiffness in pre-apoptotic colon and pancreatic cancer cells via localized F-actin polymerization in the apical cortex — independent of changes in total F-actin levels. Using atomic force microscopy and flow cytometry, we demonstrate this effect across multiple ROS inducers: the combination of arsenic trioxide and D-enantiomer of vitamin C, hydrogen peroxide, and rotenone. These findings explain previously debated relationships on how ROS influence actin organization, which may affect cellular stiffness. By separating total from cortical actin effects, our study reveals a redox-sensitive mechanism that governs cytoskeletal remodelling and may impair cancer cell migration.