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Pharmacodynamic characterization and evaluation of oxidative stress effects of digitoxigenin derivatives on HeLa cells

Authors: Jessica M. M. Valadares,Pedro Azalim-Neto,Xiaofan Liu,Nathallia Cavalcanti Carrozza,George A. O’Doherty,Luis Eduardo M. Quintas,Leandro A. Barbosa
Publisher: Springer Science and Business Media LLC
Publish date: 2025-1-15
ISSN: 0022-2631,1432-1424 DOI: 10.1007/s00232-024-00334-z
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The findings suggest that oxidative stress plays a central role in the cytotoxicity of digitoxigenin derivatives, yet the study does not establish whether this effect is a direct consequence of Na+/K+-ATPase inhibition or an off-target mechanism. Were rescue experiments using antioxidants or Na+/K+-ATPase activators conducted to confirm the causal link between oxidative stress and cytotoxicity? Additionally, while the study reports increased lipid peroxidation, it does not explore downstream consequences such as membrane integrity loss or apoptotic signaling. Could these aspects be further investigated to provide a more comprehensive mechanistic understanding of digitoxigenin-induced cell death?

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