The proliferation effects of fluoxetine and amitriptyline on human breast cancer cells and the underlying molecular mechanisms

Lei, Bingli; Xu, Lanbing; Zhang, Xiaolan; Peng, Wei; Tang, Qianqian; Feng, Chenglian

doi:10.1016/j.etap.2021.103586

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…In a study with diabetic rats, fluoxetine was reported to regulate lipid metabolism via the PI3K/AKT signaling pathway [ 63 ]. Lei et al reported that fluoxetine increased the proliferation of breast cancer cells by inducing low concentrations of PI3K/AKT signals in SKBR3 and MCF-7 breast cancer cells [ 64 ]. In our study, we also found that PI3K was another target of fluoxetine during its anti-inflammatory activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

Immunostimulatory activity of fluoxetine in macrophages via regulation of the PI3K and P38 signaling pathways

2022

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Fluoxetine is an antidepressant drug that is heavily preferred in the cure of depression, which is from the selective serotonin reuptake inhibitor (SSRI) group. There are many reports on the effect of fluoxetine on the immune system, and its effect on the macrophage cells has never been looked at before. We aimed to demonstrate the cytokine production potential of fluoxetine antidepressant, which is widely used in the clinic, in the J774.2 cell line and its effect on PI3K and P38 pathways. The use of fluoxetine alone in J774.2 macrophage cells showed immunostimulatory properties by inducing the production of tumor necrosis factor-α (TNF-α), interleukin (IL) IL-6, IL-12p40, and granulocyte–macrophage colony-stimulating factor (GM-CSF) cytokines. It showed anti-inflammatory properties by completely stopping the production of cytokines (IL-6, IL12p40, TNF-α, and GM-CSF) at all concentrations where LPS and fluoxetine were used together. While PI3K and P38 pathways were not effective in the immunostimulatory effect in the presence of the drug agent, we found that the PI3K and P38 pathways were influenced during their anti-inflammatory activity.

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Section: Discussionmentioning

confidence: 99%

Immunostimulatory activity of fluoxetine in macrophages via regulation of the PI3K and P38 signaling pathways

2022

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“…Tricyclic antidepressants and their analogs are among the most well-studied repurposed drugs for cancer therapy. They have exhibited excellent efficacy in halting cancer cell growth and metastasis [ 403 – 406 ]. Interestingly, the antitumor efficacy of imipramine and amitriptyline primarily relies on their metabolic modulating ability in restoring the proper function of mitochondria, which differs from those functioning through disturbing mitochondria [ 407 ].…”

Section: Strategies For Overcoming Mitochondria-targeting Bottlenecks...mentioning

confidence: 99%

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

et al. 2022

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Drug resistance represents a major obstacle in cancer management, and the mechanisms underlying stress adaptation of cancer cells in response to therapy-induced hostile environment are largely unknown. As the central organelle for cellular energy supply, mitochondria can rapidly undergo dynamic changes and integrate cellular signaling pathways to provide bioenergetic and biosynthetic flexibility for cancer cells, which contributes to multiple aspects of tumor characteristics, including drug resistance. Therefore, targeting mitochondria for cancer therapy and overcoming drug resistance has attracted increasing attention for various types of cancer. Multiple mitochondrial adaptation processes, including mitochondrial dynamics, mitochondrial metabolism, and mitochondrial apoptotic regulatory machinery, have been demonstrated to be potential targets. However, recent increasing insights into mitochondria have revealed the complexity of mitochondrial structure and functions, the elusive functions of mitochondria in tumor biology, and the targeting inaccessibility of mitochondria, which have posed challenges for the clinical application of mitochondrial-based cancer therapeutic strategies. Therefore, discovery of both novel mitochondria-targeting agents and innovative mitochondria-targeting approaches is urgently required. Here, we review the most recent literature to summarize the molecular mechanisms underlying mitochondrial stress adaptation and their intricate connection with cancer drug resistance. In addition, an overview of the emerging strategies to target mitochondria for effectively overcoming chemoresistance is highlighted, with an emphasis on drug repositioning and mitochondrial drug delivery approaches, which may accelerate the application of mitochondria-targeting compounds for cancer therapy.

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“…The anticancer properties of fluoxetine were confirmed in many cancer models, both in vitro and in vivo [98,99]. However, some recent studies support its pro-survival potential as well [100,101]. An example of antiarrhythmic agents that can be potentially used in anticancer therapy is verapamil.…”

Section: Anticancer Therapies Targeting Ion Channelsmentioning

confidence: 98%

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

et al. 2021

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Modifications of the composition or organization of the cancer cell membrane seem to be a promising targeted therapy. This approach can significantly enhance drug uptake or intensify the response of cancer cells to chemotherapeutics. There are several methods enabling lipid bilayer modifications, e.g., pharmacological, physical, and mechanical. It is crucial to keep in mind the significance of drug resistance phenomenon, ion channel and specific receptor impact, and lipid bilayer organization in planning the cell membrane-targeted treatment. In this review, strategies based on cell membrane modulation or reorganization are presented as an alternative tool for future therapeutic protocols.

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The proliferation effects of fluoxetine and amitriptyline on human breast cancer cells and the underlying molecular mechanisms

Cited by 10 publications

References 42 publications

Immunostimulatory activity of fluoxetine in macrophages via regulation of the PI3K and P38 signaling pathways

Immunostimulatory activity of fluoxetine in macrophages via regulation of the PI3K and P38 signaling pathways

Mitochondrial adaptation in cancer drug resistance: prevalence, mechanisms, and management

Modifications of Plasma Membrane Organization in Cancer Cells for Targeted Therapy

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