In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma

Biber, Ayşenur; Durusu, Ipek Zeynep; Özen, Can

doi:10.3906/biy-1802-11

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…Thus, it is the first evidence of the positive effects of repair and activation of adaptation mechanisms to stress conditions. Others also indicate a cycle arrest in the G2/M phase or S, suggesting that antidepressants can exhibit cytotoxic properties and induce apoptotic cell death possibly via a mitochondrial independent pathway [ 21 , 22 ]. In turn, cell cycle arrest in the G0-G1 phase may be associated with the inhibition of cyclin D2 activity in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

Sołek

Mytych

Tabęcka-Łonczyńska

et al. 2021

IJMS

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The incidence of depression among humans is growing worldwide, and so is the use of antidepressants. However, our fundamental understanding regarding the mechanisms by which these drugs function and their off-target effects against human sexuality remains poorly defined. The present study aimed to determine their differential toxicity on mouse spermatogenic cells and provide mechanistic data of cell-specific response to antidepressant and neuroleptic drug treatment. To directly test reprotoxicity, the spermatogenic cells (GC-1 spg and GC-2 spd cells) were incubated for 48 and 96 h with amitriptyline (hydrochloride) (AMI), escitalopram (ESC), fluoxetine (hydrochloride) (FLU), imipramine (hydrochloride) (IMI), mirtazapine (MIR), olanzapine (OLZ), reboxetine (mesylate) (REB), and venlafaxine (hydrochloride) (VEN), and several cellular and biochemical features were assessed. Obtained results reveal that all investigated substances showed considerable reprotoxic potency leading to micronuclei formation, which, in turn, resulted in upregulation of telomeric binding factor (TRF1/TRF2) protein expression. The TRF-based response was strictly dependent on p53/p21 signaling and was followed by irreversible G2/M cell cycle arrest and finally initiation of apoptotic cell death. In conclusion, our findings suggest that antidepressants promote a telomere-focused DNA damage response in germ cell lines, which broadens the established view of antidepressants’ and neuroleptic drugs’ toxicity and points to the need for further research in this topic with the use of in vivo models and human samples.

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Section: Discussionmentioning

confidence: 99%

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

Sołek

Mytych

Tabęcka-Łonczyńska

et al. 2021

IJMS

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“…Regarding tricyclic antidepressants, nortriptyline has shown anticancer effects, particularly in PC, because it inhibits cell proliferation and induces apoptosis due to increased intracellular calcium in PC cells and induces cytotoxicity through cell cycle interruption by inhibition of CDK1 and by inhibiting Rb expression, affecting the Rb/E2F complex and, consequently, inhibiting the expression of E2F target genes, since Rb phosphorylation must occur for E2F to be separated from the Rb/E2F complex and activate the expression of genes required for the S-phase transition [ 40 , 41 , 42 ].…”

Section: Pharmacotherapeutic Groups With Potential Efficacy In Pc Tre...mentioning

confidence: 99%

Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer

Lourenço

Vale

2023

IJMS

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Worldwide, prostate cancer (PC) is the second most frequent cancer among men and the fifth leading cause of death; moreover, standard treatments for PC have several issues, such as side effects and mechanisms of resistance. Thus, it is urgent to find drugs that can fill these gaps, and instead of developing new molecules requiring high financial and time investments, it would be useful to select non-cancer approved drugs that have mechanisms of action that could help in PC treatment, a process known as repurposing drugs. In this review article, drugs that have potential pharmacological efficacy are compiled to be repurposed for PC treatment. Thus, these drugs will be presented in the form of pharmacotherapeutic groups, such as antidyslipidemic drugs, antidiabetic drugs, antiparasitic drugs, antiarrhythmic drugs, anti-inflammatory drugs, antibacterial drugs, antiviral drugs, antidepressant drugs, antihypertensive drugs, antifungal drugs, immunosuppressant drugs, antipsychotic drugs, antiepileptic and anticonvulsant drugs, bisphosphonates and drugs for alcoholism, among others, and we will discuss their mechanisms of action in PC treatment.

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“…Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiple myeloma (MM) treatment. The TCA nortriptyline has shown greater inhibitory and apoptotic effects in U266 MM cells than cisplatin; however, the cisplatin-nortriptyline combination also indicated strong antagonism [92]. Ten years ago, in vitro and in silico studies demonstrated that amitriptyline showed anti-myeloma ac-tivity by inducing cell apoptosis through the inhibition of histone deacetylases [90].…”

Section: Multiple Myelomamentioning

confidence: 99%

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment

Asensi-Cantó

López-Abellán

Castillo-Guardiola

et al. 2022

Cancers

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Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs’ safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in the clinical setting. The current evidence points out that TCAs are safe and beneficial to treat neuropathic pain associated with cancer and chemotherapy, and they block different molecular pathways used by cancer cells from different locations for tumor growth and promotion. Likewise, ongoing clinical trials evaluating the antineoplastic effects of TCAs are discussed. TCAs are very biologically active compounds, and their repurposing as antitumoral drugs is a promising and straightforward approach to treat specific cancer subtypes and to further define their molecular targets, as well as an interesting starting point to design analogues with increased antitumoral activity.

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In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma

Cited by 13 publications

References 27 publications

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

Molecular Consequences of Depression Treatment: A Potential In Vitro Mechanism for Antidepressants-Induced Reprotoxic Side Effects

Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment

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