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Sertraline and cancer

William D Gwynne, Robin M Hallett, Adele Girgis-Gabardo, Bojana Bojovic, Anna Dvorkin-Gheva, Craig Aarts, Kay Dias, Anita Bane, John A Hassell
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype...
March 29, 2017: Oncotarget
Di Xia, Ying-Ting Zhang, Gui-Ping Xu, Wei-Wei Yan, Xiao-Rong Pan, Jian-Hua Tong
It has been found that sertraline, a widely used antidepressant drug, possessed antitumor roles in a variety of cancers including liver cancer, colorectal cancer and lymphoma. In this study, we provided evidences that sertraline had potent antiproliferative activity not only in acute myeloid leukemia (AML) cell lines but also in the fresh leukemia cells from AML patients, and could induce cell death through both apoptosis and autophagy pathways. Moreover, we found that inhibiting autophagy pathway could partially attenuate sertraline-induced apoptosis and cell growth inhibition, indicating that sertraline-induced autophagy process could facilitate AML cell apoptosis to some degree...
February 13, 2017: Leukemia & Lymphoma
Daniel P Radin, Parth Patel
Current cancer research strongly focuses on identifying novel pathways that can be selectively exploited in the clinic and identifying drugs capable of exploiting cancer vulnerabilities. Occasionally, drugs identified to exploit a cancer-specific vulnerability are on the market for clinical indications in another disease area. Rebranding them as anti-cancer drugs is a process commonly referred to as drug repurposing and is typically a faster method than bringing a novel drug to market. Selective serotonin reuptake inhibitors (SSRIs) are primarily used for treating several types of depression, but over the past two decades mounting evidence suggests that drugs in this class have oncolytic properties and reduce the risk of certain cancers...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
María Elisa Irarrázaval O, Leonardo Gaete G
Tamoxifen (Tmf), is a standard of care for women with estrogen receptor positive (ER+) breast cancer. Endoxifen is a Tmf metabolite generated by cytochrome P450 2D6 (CYP2D6). Antidepressive agents (AD) are often prescribed to women with breast cancer not only for depression, but also for anxiety and hot flashes. Some AD are substrates or inhibitors of the Tmf metabolic pathway. Therefore there may be interactions when Tmf and AD are prescribed simultaneously. Oncologic protection afforded by Tmf may become less effective or null when AD are indicated, especially in poor metabolizing patients...
October 2016: Revista Médica de Chile
Wayne A Ray, Cecilia P Chung, Katherine T Murray, Kathi Hall, C Michael Stein
OBJECTIVE: Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline. METHODS: The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011...
February 2017: Journal of Clinical Psychiatry
Linnéa Schmidt, Sathishkumar Baskaran, Patrik Johansson, Narendra Padhan, Damian Matuszewski, Lydia C Green, Ludmila Elfineh, Shimei Wee, Maria Häggblad, Ulf Martens, Bengt Westermark, Karin Forsberg-Nilsson, Lene Uhrbom, Lena Claesson-Welsh, Michael Andäng, Ida-Maria Sintorn, Bo Lundgren, Ingrid Lönnstedt, Cecilia Krona, Sven Nelander
Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures...
November 8, 2016: Oncotarget
Robin M Hallett, Adele Girgis-Gabardo, William D Gwynne, Andrew O Giacomelli, Jennifer N P Bisson, Jeremy E Jensen, Anna Dvorkin-Gheva, John A Hassell
Accumulating data suggests that the initiation and progression of human breast tumors is fueled by a rare subpopulation of tumor cells, termed breast tumor-initiating cells (BTIC), which resist radiotherapy and chemotherapy. Consequently, therapies that abrogate BTIC activity are needed to achieve durable cures for breast cancer patients. To identify such therapies we used a sensitive assay to complete a high-throughput screen of small molecules, including approved drugs, with BTIC-rich mouse mammary tumor cell populations...
August 16, 2016: Oncotarget
Gary Kelsberg, Leticia Maragh, Sarah Safranek
Selective serotonin reuptake inhibitors (SSRIs [fluoxetine, sertraline, paroxetine]) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine, as well as clonidine and gabapentin, reduce hot flashes by about 25% (approximately one per day) in women with and without a history of breast cancer. No studies compare medications against each other to determine a single best option.
May 2016: Journal of Family Practice
Desiré K Christensen, Guillermo N Armaiz-Pena, Edgardo Ramirez, Koji Matsuo, Bridget Zimmerman, Behrouz Zand, Eileen Shinn, Michael J Goodheart, David Bender, Premal H Thaker, Amina Ahmed, Frank J Penedo, Koen DeGeest, Luis Mendez, Frederick Domann, Anil K Sood, Susan K Lutgendorf
Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1...
May 31, 2016: Oncotarget
Thomas Stonier, Michael Harrison
In 2010 a population-based cohort study showed that there was decreased efficacy of the breast cancer drug tamoxifen when used in combination with fluoxetine, a commonly used SSRI antidepressant. The aim of this project was to identify patients who may be affected by this co-prescription and suggest a change in medication. The project was conducted across two GP practices in Clevedon (The Riverside Practice & The Green Practice), Bristol. The patients were all from the active patients register at each surgery...
2013: BMJ Quality Improvement Reports
Anca Pop, Diana Ioana Lupu, Julien Cherfan, Bela Kiss, Felicia Loghin
BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed classes of psychotropics. Even though the SSRI class consists of 6 molecules (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), only fluoxetine was intensively studied for endocrine disruptive effects, while the other SSRIs received less attention. This study was designed to evaluate the estrogenic/antiestrogenic effect of fluoxetine, sertraline and paroxetine...
2015: Clujul Medical (1957)
Jun Kuwahara, Takaaki Yamada, Nobuaki Egashira, Mitsuyo Ueda, Nina Zukeyama, Soichiro Ushio, Satohiro Masuda
The anti-tumor effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on several types of cancer cells have been reported. However, comparison of the anti-tumor effects of these drugs on human hepatocellular carcinoma (HepG2) cells has not been studied. We compared the anti-tumor effects of four SSRIs and two SNRIs on HepG2 cells. SSRIs and duloxetine dose-dependently decreased cell viability. Milnacipran had no effect on cell viability. The half-maximal inhibitory concentration was lower in the order of: sertraline, paroxetine, duloxetine, fluvoxamine, escitalopram, and milnacipran...
2015: Biological & Pharmaceutical Bulletin
Richard E Kast, Georg Karpel-Massler, Marc-Eric Halatsch
CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective...
September 30, 2014: Oncotarget
Velthe Drinberg, Rivka Bitcover, Wolf Rajchenbach, Dan Peer
Inherent and acquired multiple drug resistance (MDR) to chemotherapeutic drugs is a major obstacle in cancer treatment. The ATP Binding Cassettes (ABC) transporter super family that act as extrusion pumps such as P-glycoprotein and multidrug-resistance-associated-proteins have prominent roles in cancer MDR. One of the most efficient strategies to modulate this active drug efflux from the cells is to physically block the pump proteins and thus change the balance between drug influx and efflux toward an accumulation of drug inside the cell, which eventually cumulates into cell death...
November 28, 2014: Cancer Letters
Jing Chen, Chuancheng Chen, Shengli Zhi
BACKGROUND: Laryngectomy, a common treatment for laryngeal cancer, is a disabling operation that can induce tremendous stress, but little is known about how to alleviate the psychological effects of the operation. AIM: Compare the effectiveness of cognitive behavioral therapy (CBT) and medication in treating anxiety and depression among throat cancer patients after laryngectomy. METHODS: Review of medical records of the psychological outpatient clinic in the Third People's Hospital of Huzhou City between March 2009 and May 2013 identified 63 patients with post-laryngectomy depression or anxiety disorders who received 8 weeks of one-on-one treatment with CBT (in which patients responded in writing because they were unable to speak) and 56 patients who received 8 weeks of treatment with buspirone (n=11), sertraline (n=9) or both busipirone and sertraline (n=36)...
April 2014: Shanghai Archives of Psychiatry
Xu-Juan Li, Zhi-Yuan Dai, Bei-Ying Zhu, Jia-Ping Zhen, Wen-Fu Yang, De-Qiang Li
BACKGROUND: The aim of this study was to investigate effects of the antidepressant sertraline on executive function and quality of life in patients with advanced cancer. MATERIAL/METHODS: We assigned 122 patients with stage III or IV cancer to the depressed group (DG, n=86) or the non-depressed group (NG, n=36). All subjects were given supportive treatment and patients in the DG received additional antidepressant treatment. RESULTS: There were significant differences in total scores of the Hamilton anxiety scale (HAMA) and the Hamilton depression scale (HAMD), performance in the Wisconsin card sorting test, and SF-36 domains...
July 22, 2014: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
M Kesim, M N Yanik, M Kadioglu, D Pepeoglu, I Erkoseoglu, N I Kalyoncu, E Yaris
INTRODUCTION: Antidepressant drugs are used in the treatment of pain as an adjuvant or alone. It has been shown that antidepressant drugs have analgesic effects in various diseases (diabetic neuropathy, low back pain, cancer pain etc.) Sertraline is a potent serotonin re-uptake inhibitor. Some antidepressant drugs inhibited both of the reuptake of serotonin and of noradrenaline. These drugs are called serotonin-noradrenaline re-uptake inhibitors (SNRIs). Milnacipran is a serotonin-noradrenaline re-uptake inhibitor...
2014: Bratislavské Lekárske Listy
Murat Ozturk, Selcuk Ucar, Fatih Sarı, Selvet Erdogan, Murat Topdag, Mete Iseri
BACKGROUND/OBJECTIVE: Cisplatin is a widely used chemotherapeutic agent, but its ototoxicity side effect can occur in the majority of patients. Lots of agents were tried to prevent this, but there is not a routine treatment modality yet. The aim of this study was to evaluate the otoprotective effect of sertraline, which is an antidepressant with neuroprotective effects, against cisplatin, in rats. DESIGN: Experimental animal study. MATERIAL AND METHODS: Forty-eight rats were randomly separated in two groups as groups I and II...
2013: TheScientificWorldJournal
Richard E Kast, John A Boockvar, Ansgar Brüning, Francesco Cappello, Wen-Wei Chang, Boris Cvek, Q Ping Dou, Alfonso Duenas-Gonzalez, Thomas Efferth, Daniele Focosi, Seyed H Ghaffari, Georg Karpel-Massler, Kirsi Ketola, Alireza Khoshnevisan, Daniel Keizman, Nicolas Magné, Christine Marosi, Kerrie McDonald, Miguel Muñoz, Ameya Paranjpe, Mohammad H Pourgholami, Iacopo Sardi, Avishay Sella, Kalkunte S Srivenugopal, Marco Tuccori, Weiguang Wang, Christian R Wirtz, Marc-Eric Halatsch
To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth...
April 2013: Oncotarget
Sylvain L'Espérance, Suzanne Frenette, Anne Dionne, Jean-Yves Dionne
PURPOSE: Breast cancer patients frequently report hot flashes. Given that conventional hormone replacement therapy is generally contraindicated for them, other therapeutic modalities must be considered. The purpose of this review was to develop evidence-based recommendations on non-hormonal pharmacological interventions, including natural health products, for managing hot flashes in women undergoing treatment for breast cancer or with a history of breast cancer. METHODS: A review of the scientific literature published between January 2000 and December 2011 was performed...
May 2013: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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