Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment

Asensi-Cantó, Antonio; López-Abellán, María Dolores; Castillo-Guardiola, Verónica; Hurtado, Ana María; Martínez-Penella, Mónica; Luengo‐Gil, Ginés; Conesa‐Zamora, Pablo

doi:10.3390/cancers14133248

Cited by 7 publications

(2 citation statements)

References 131 publications

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“…It is critical to develop efficient anti-GC medicines for advanced-stage patients. Numerous studies have demonstrated that tricyclic antidepressants such as imipramine, amitriptyline, and clomipramine have significant antitumor effects 28 . The existing treatment methods and drug discovery methods are being used in a novel way, namely, drug repurposing.…”

Section: Discussionmentioning

confidence: 99%

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

Zhu,

Lu,

Wang

et al. 2024

Sci Rep

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Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.

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Section: Discussionmentioning

confidence: 99%

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

Zhu,

Lu,

Wang

et al. 2024

Sci Rep

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“…Their effectiveness has been proven in the treatment of postherpetic neuralgia, central postpartum pain, pain after spinal cord injury and nerve injury [ 105 , 108 ]. Recent studies have reported that TCAs also exhibit antitumoral effects and may be useful for the treatment of neuropathic pain associated with neoplastic disorders [ 155 ]. The exact mechanism underlying the analgesic properties of TCAs remains unclear.…”

Section: Treatment Strategies For Neuropathic Painmentioning

confidence: 99%

Diagnosis and Management of Neuropathic Pain in Spine Diseases

Bielewicz

Kamieniak

Szymoniuk

et al. 2023

JCM

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Neuropathic pain is generally defined as a non-physiological pain experience caused by damage to the nervous system. It can occur spontaneously, as a reaction to a given stimulus, or independently of its action, leading to unusual pain sensations usually referred to as firing, burning or throbbing. In the course of spine disorders, pain symptoms commonly occur. According to available epidemiological studies, a neuropathic component of pain is often present in patients with spinal diseases, with a frequency ranging from 36% to 55% of patients. Distinguishing between chronic nociceptive pain and neuropathic pain very often remains a challenge. Consequently, neuropathic pain is often underdiagnosed in patients with spinal diseases. In reference to current guidelines for the treatment of neuropathic pain, gabapentin, serotonin and norepinephrine reuptake inhibitors and tricyclic antidepressants constitute first-line therapeutic agents. However, long-term pharmacologic treatment often leads to developing tolerance and resistance to used medications. Therefore, in recent years, a plethora of therapeutic methods for neuropathic pain have been developed and investigated to improve clinical outcomes. In this review, we briefly summarized current knowledge about the pathophysiology and diagnosis of neuropathic pain. Moreover, we described the most effective treatment approaches for neuropathic pain and discussed their relevance in the treatment of spinal pain.

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Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with >14,000 cases from Denmark and Sweden

Zheng,

Baandrup,

Wang

et al. 2024

Maturitas

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Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment

Cited by 7 publications

References 131 publications

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway

Diagnosis and Management of Neuropathic Pain in Spine Diseases

Antidepressant use and ovarian cancer risk: Evidence from nationwide studies with >14,000 cases from Denmark and Sweden

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