Antidepressant fluoxetine and its potential against colon tumors

Stopper, Helga; Garcia, Sérgio Britto; Waaga-Gasser, Ana Maria; Kannen, Vinicius

doi:10.4251/wjgo.v6.i1.11

Cited by 21 publications

(14 citation statements)

References 97 publications

(177 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 75%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 75%

Fluoxetine regulates cell growth inhibition of interferon-α

Lin¹,

Chiu

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…In some clinical studies, a 50% reduction of risk of colon cancer was reported in patients treated with fluoxetine (Coogan et al, 2009). Various animal studies also supported a reduction in colon cancer incidence and many different signalling pathways such as NF-κB, ROS formation and cell cycle arrest were reported as the likely mechanisms of action in a variety of different carcinoma cells (Koh et al, 2011;Tutton & Barkla, 1986;Kannen et al, 2011Kannen et al, , 2012Lee et al, 2010, Krishnan et al, 2008Stopper et al, 2014).…”

Section: Introductionmentioning

confidence: 96%

Fluoxetine selectively induces p53-independent apoptosis in human colorectal cancer cells

Marcinkute

Afshinjavid

Fatokun

et al. 2019

European Journal of Pharmacology

View full text Add to dashboard Cite

Fluoxetine has been shown to induce anti-tumour activity. The aim of this study was to determine the effect of fluoxetine on HCT116+/+ and p53 gene-depleted HCT116-/-human colorectal cancer cells and the mechanisms, including potential p53-dependence, of its action. Fluoxetine-induced apoptosis was investigated by mitochondrial membrane potential assay, Annexin V assay, two-step cell cycle analysis using NC-3000™ system and pharmacological inhibition assays. Fluoxetine induced very selectively concentration-dependent apoptosis in human colorectal cancer cells by altering mitochondrial membrane potential and inducing translocation of phosphatidylserine to the outer membrane layer. Further evidence of the preponderance of apoptosis in fluoxetine-induced cell death is provided by the finding that the cell death was not blocked by inhibitors of parthanatos, a form of cell death that results from overactivation of the enzyme poly (ADP-ribose) polymerase (PARP) but is different from apoptosis. Data obtained indicate fluoxetine caused cell cycle event at Sub-G1 and G0/G1 phases in both cell lines. In terms of apoptosis, there is no significant difference between the responses of the two cell lines to fluoxetine. In conclusion, fluoxetine's cytotoxicity induces mainly apoptosis and causes DNA fragmentation in human colorectal cancer cells, which seemed to be independent of the p53 protein, as no significant difference in death profiles in response to fluoxetine treatment was observed in both the p53-intact and the p53-deleted cell lines. Fluoxetine, therefore, has potential for being repurposed as a drug for the treatment of colon cancer and thus deserves further investigations in this context.

show abstract

“…Moreover, paroxetine induces cell apoptosis through MET and ERBB3 inhibition, leading to the induction of the JNK and caspase-3 pathways and the reduction of the expression of antiapoptotic protein Bcl-2 [ 62 , 63 ]. On the other hand, fluoxetine showed an antiproliferative effect on colon cancer cells by the reduction of VEGF expression [ 64 ] and by the alteration of tumour-related energy generation machinery [ 65 ], especially under conditions of hypoxia. Recently, Marcinkute et al confirmed fluoxetine’s cytotoxicity in human colon cancer cells through p53-independent apoptosis [ 66 ].…”

Section: Resultsmentioning

confidence: 99%

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Cantini

Giglio

Bittoni

et al. 2020

Cancers

View full text Add to dashboard Cite

Colorectal cancer is characterized by high incidence worldwide. Despite increased awareness and early diagnosis thanks to screening programmes, mortality remains high, particularly for patients with metastatic involvement. Immune checkpoint inhibitors or poly (ADP-ribose) polymerase (PARP)-inhibitors have met with disappointing results when used in this setting, opposed to other malignancies. New drugs with different mechanisms of action are needed in this disease. Drug repurposing might offer new therapeutic options, as patients with metastatic colorectal cancer often share risk factors for other chronic diseases and thus frequently are on incidental therapy with these drugs. The aim of this review is to summarise the published results of the activity of drugs used to treat chronic medications in patients affected by colorectal cancer. We focused on antihypertensive drugs, Non-Steroid Anti-inflammatory Drugs (NSAIDs), metformin, antidepressants, statins and antibacterial antibiotics. Our review shows that there are promising results with beta blockers, statins and metformin, whereas data concerning antidepressants and antibacterial antibiotics seem to show a potentially harmful effect. It is hoped that further prospective trials that take into account the role of these drugs as anticancer medications are conducted.

show abstract

Antidepressant fluoxetine and its potential against colon tumors

Cited by 21 publications

References 97 publications

Fluoxetine regulates cell growth inhibition of interferon-α

Fluoxetine regulates cell growth inhibition of interferon-α

Fluoxetine selectively induces p53-independent apoptosis in human colorectal cancer cells

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

Contact Info

Product

Resources

About