RRC ID 82588
Author Adornetto A, Laganà ML, Satriano A, Licastro E, Corasaniti MT, Bagetta G, Russo R.
Title The Antidepressant Drug Amitriptyline Affects Human SH-SY5Y Neuroblastoma Cell Proliferation and Modulates Autophagy.
Journal Int J Mol Sci
Abstract Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and is prescribed off-label for several neurological conditions like neuropathic pain, migraines and anxiety. Besides their action on the reuptake of monoaminergic neurotransmitters, tricyclic antidepressants interact with several additional targets that may contribute to either therapeutic or adverse effects. Here, we investigated the effects of amitriptyline on proliferation and autophagy (i.e., an evolutionarily conserved catabolic pathway responsible for the degradation and recycling of cytoplasmic material) in human SH-SY5Y neuroblastoma cell cultures. The dose and time-dependent upregulation of the autophagy marker LC3II and the autophagy receptor p62, with the accumulation of LAMP1 positive compartments, were observed in SH-SY5Y cells exposed to the amitriptyline. These effects were accompanied by reduced cell viability and decreased clonogenic capacity, without a significant induction of apoptosis. Decrease viability and clonogenic activity were still observed in autophagy deficient Atg5-/- MEF and following pre-treatment of SH-SY5Y culture with the autophagy inhibitor chloroquine, suggesting that they were independent from autophagy modulation. Our findings demonstrate that amitriptyline acts on pathways crucial for cell and tissue homeostasis (i.e., autophagy and proliferation) and pose the basis for further studies on the potential therapeutic application of amitriptyline, as well as the consequences of its use for long-term treatments.
Volume 25(19)
Published 2024-9-27
DOI 10.3390/ijms251910415
PII ijms251910415
PMID 39408742
PMC PMC11476963
MeSH Amitriptyline* / pharmacology Antidepressive Agents / pharmacology Antidepressive Agents, Tricyclic / pharmacology Apoptosis / drug effects Autophagy* / drug effects Cell Line, Tumor Cell Proliferation* / drug effects Cell Survival / drug effects Humans Neuroblastoma* / drug therapy Neuroblastoma* / metabolism Neuroblastoma* / pathology
IF 4.556
Resource
Human and Animal Cells Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711)