Inhibitory effect of antidepressants on B16F10 melanoma tumor growth

Grygier, Beata; Arteta, Beatriz; Kubera, Marta; Basta‐Kaim, Agnieszka; Budziszewska, Bogusława; Leśkiewicz, Monika; Curzytek, Katarzyna; Duda, Weronika; Lasoń, Władysław; Maes, Michaël

doi:10.1016/s1734-1140(13)71045-4

Cited by 31 publications

(22 citation statements)

References 38 publications

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“…Thus, fluoxetine administration after B16F10 melanoma cells injection dramatically inhibited solid tumor growth 88 , whereas chronic pretreatment with fluoxetine or desipramine before melanoma cells inoculation dramatically promoted metastasis formation and increased mortality rate in highly active young male and female animals by impairing the efficiency of anti-tumor immunity and enhancing the implantation efficiency of melanoma cells 89 …”

Section: Use Of Antidepressants and Cancermentioning

confidence: 99%

Depression in cancer: The many biobehavioral pathways driving tumor progression

Bortolato

Hyphantis

Valpione

et al. 2017

Cancer Treatment Reviews

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243

179

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Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote:(1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitary-adrenal axis. Consequently, the prompt recognition of depression among patients with cancer who may benefit of treatment strategies targeting depressive symptoms, cognitive dysfunction, fatigue and sleep disturbances, is a public health priority. Moreover, behavioral strategies aiming at reducing psychological distress and depressive symptoms, including addressing unhealthy diet and life-style choices, as well as physical inactivity and sleep dysfunction, may represent important strategies not only to treat depression, but also to improve wider cancer-related outcomes. Herein, we provide a comprehensive review of the intertwined biobehavioural pathways linking depression to cancer progression. In addition, the clinical implications of these findings are critically reviewed.

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Section: Use Of Antidepressants and Cancermentioning

confidence: 99%

Depression in cancer: The many biobehavioral pathways driving tumor progression

Bortolato

Hyphantis

Valpione

et al. 2017

Cancer Treatment Reviews

Self Cite

243

179

View full text Add to dashboard Cite

show abstract

“…While the role of serotonergic system in cancer patients has not been largely studied, advanced stages of breast cancer correlate with increased levels of systemic 5-HT [ 248 ]. In mouse models of melanoma and lymphoma, SSRI treatment reduced tumor growth by 50%, inhibited IL-10 and IFN- γ production, and increased IL-1 β production [ 249 ]. Similarly, exposing a Burkitt's lymphoma cell line to different SSRIs (fluoxetine, paroxetine, or citalopram) decreased DNA synthesis and induced cell death [ 250 ].…”

Section: Changes To the Serotonergic System Affect Immune Responsementioning

confidence: 99%

Immunomodulatory Effects Mediated by Serotonin

Arreola

Becerril-Villanueva²,

Cruz-Fuentes

et al. 2015

Journal of Immunology Research

146

128

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Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

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“…Indeed, fluoxetine has been shown to induce cell death in cancer cells in vitro [3–11] and to prevent the growth of tumors in vivo [5, 12–14]. Fluoxetine reduces cell viability in various models of cancer.…”

Section: Introductionmentioning

confidence: 99%

The antidepressant fluoxetine induces necrosis by energy depletion and mitochondrial calcium overload

et al. 2016

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Selective Serotonin Reuptake Inhibitor antidepressants, such as fluoxetine (Prozac), have been shown to induce cell death in cancer cells, paving the way for their potential use as cancer therapy. These compounds are able to increase cytosolic calcium concentration ([Ca2+]cyt), but the involved mechanisms and their physiological consequences are still not well understood. Here, we show that fluoxetine induces an increase in [Ca2+]cyt by emptying the endoplasmic reticulum (ER) through the translocon, an ER Ca2+ leakage structure. Our data also show that fluoxetine inhibits oxygen consumption and lowers mitochondrial ATP. This latter is essential for Ca2+ reuptake into the ER, and we postulated therefore that the fluoxetine-induced decrease in mitochondrial ATP production results in the emptying of the ER, leading to capacitative calcium entry. Furthermore, Ca2+ quickly accumulated in the mitochondria, leading to mitochondrial Ca2+ overload and cell death. We found that fluoxetine could induce an early necrosis in human peripheral blood lymphocytes and Jurkat cells, and could also induce late apoptosis, especially in the tumor cell line. These results shed light on fluoxetine-induced cell death and its potential use in cancer treatment.

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Inhibitory effect of antidepressants on B16F10 melanoma tumor growth

Cited by 31 publications

References 38 publications

Depression in cancer: The many biobehavioral pathways driving tumor progression

Depression in cancer: The many biobehavioral pathways driving tumor progression

Immunomodulatory Effects Mediated by Serotonin

The antidepressant fluoxetine induces necrosis by energy depletion and mitochondrial calcium overload

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