Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1

Krishnan, Anand; Hariharan, Ramkumar; Nair, S. Asha; Pillai, M. Radhakrishna

doi:10.1016/j.bcp.2008.02.013

Cited by 65 publications

(58 citation statements)

References 40 publications

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“…Instead, fluoxetine itself caused a slight G1 arrest along with a marked induction of p27 as well as slight reduction of cyclin D1 and p53. Our results were similar to previous studies related to the effect of fluoxetine on G1 arrest and upregulations of p27 in human cervical cancer cells (SiHa), breast cancer cells (MDA-MB-231) and colon cancer cells HT29 (28)(29)(30). In addition, the dosage of fluoxetine as a chemosensitizer is kept under the range of 5-20 µM, where this agent itself does not affect cell viability (15).…”

Section: Discussionsupporting

confidence: 90%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

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Abstract. Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

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Section: Discussionsupporting

confidence: 90%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

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“…Comparing those reports that describe how FLX modulates tumor metabolism [49,50,[52][53][54][55] with others describing its activity against tumor growth [40,58,[87][88][89][90][91][92] , it becomes clear that FLX blocks tumor cell proliferation by impairing the malignant energy generation. The anti-tumor proliferative effects of FLX [40,56,92,93] have been related to different causes, such as delays in cell-cycle progression by inhibiting DNA synthesis and also to a possible binding directly to DNA via groove mode and high attraction force [58,[87][88][89][90]94] .…”

Section: Flx Reduces Preneoplastic Lesions Acting On Colonic Microenvmentioning

confidence: 99%

“…The anti-tumor proliferative effects of FLX [40,56,92,93] have been related to different causes, such as delays in cell-cycle progression by inhibiting DNA synthesis and also to a possible binding directly to DNA via groove mode and high attraction force [58,[87][88][89][90]94] . On a molecular level, FLX was shown to arrest breast tumor cells at G0/G1 phase by disrupting skp2-CKS1 assembly, which is required to enable cell cycle progression [91] . Recent reports have been supporting the idea of FLX acting against tumor proliferating cells by reducing c-Myc and cyclins (D1, D3, E, B and A), whereas cell-cycle checkpoints (p15, p16, p21, p27 and p53) were enhanced [40,91,92] …”

Section: Flx Reduces Preneoplastic Lesions Acting On Colonic Microenvmentioning

confidence: 99%

Antidepressant fluoxetine and its potential against colon tumors

Stopper

Garcia

Waaga-Gasser

et al. 2014

WJGO

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Colon cancer is one of the most common tumors worldwide, with increasing incidence in developing countries. Patients treated with fluoxetine (FLX) have a reduced incidence of colon cancer, although there still remains great controversy about the nature of its effects. Here we explore the latest achievements related to FLX treatment and colon cancer. Moreover, we discuss new ideas about the mechanisms of the effects of FLX treatment in colon cancer. This leads to the hypothesis of FLX arresting colon tumor cells at the at G1 cell-cycle phase through a control of the tumor-related energy generation machinery. We believe that the potential of FLX to act against tumor metabolism warrants further investigation. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved. Key words: Fluoxetine; Colon cancer; Cancer therapy; Tumor metabolismCore tip: It is currently thought that aerobic glycolysis is key for understanding cell survival in the hostile tumor microenvironment. Then, the antidepressant fluoxetine (FLX) has been shown to reduce colon tumor growth in animals and colon cancer incidence in humans. Here, we explore new perspectives of FLX reducing the development of colon tumors through a blockage in tumor metabolism. This perspective review is based on our current unpublished experimental dataset which shows FLX as a potential co-chemotherapeutic agent for colon cancer therapy.Stopper H, Garcia SB, Waaga-Gasser AM, Kannen V. Antidepressant fluoxetine and its potential against colon tumors.

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“…Krishnan et al (2008) showed that fluoxetine is cytotoxic to tumor cell lines (human cervical cancer and breast cancer cells) and tumor-derived primary fibroblasts, inducing loss of viability mediated through apoptotic pathways. In another study, Kusakawa et al (2008) proposed an association between an increase in major malformations by a mouse embryonic stem cell and the maternal use of SSRIs, such as fluoxetine, during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems

Düsman¹,

Almeida²,

Mariucci³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Fluoxetine, commonly known as Prozac, is the first representative of the so-called new generation of antidepressants that promise efficacy, with few side effects, against deep depression, nervous bulimia, and anxiety. As there is a growing number of people suffering from anxiety and depression; consequently, the use of fluoxetine is also increasing. Verifying absence of drug effects such as cytotoxicity or mutagenicity is of great importance. Certain vitamins, such as vitamin A (retinol, retinoids) and vitamin C (ascorbic acid) protect and are extremely active against mutagens. We evaluated the cytotoxic and mutagenic activity of fluoxetine, with and without concomitant administration of vitamin A or C, in Allium cepa meristem cells and Wistar rat bone marrow cells. The A. cepa meristem cells Cytotoxicity and mutagenicity of fluoxetine showed fluoxetine cytotoxicity; concomitant treatment with vitamin A or C proved non-protective. Treatment of Wistar rats with fluoxetine intraperitoneally or via gavage did not affect cell division or cause clastogenic effects. Vitamin A and C did not affect the cytotoxicity or mutagenicity of fluoxetine in the rat cells.

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Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1

Cited by 65 publications

References 40 publications

Fluoxetine regulates cell growth inhibition of interferon-α

Fluoxetine regulates cell growth inhibition of interferon-α

Antidepressant fluoxetine and its potential against colon tumors

Cytotoxicity and mutagenicity of fluoxetine hydrochloride (Prozac), with or without vitamins A and C, in plant and animal model systems

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