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Escitalopram oxalate, a selective serotonin reuptake inhibitor, exhibits cytotoxic and apoptotic effects in glioma C6 cells

Published online by Cambridge University Press:  24 June 2014

Miriş Dikmen ,
Zerrin Cantürk  and
Yusuf Öztürk
Miriş Dikmen*
Affiliation:
Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eskisehir, Turkey
Zerrin Cantürk
Affiliation:
Faculty of Pharmacy, Department of Pharmaceutical Microbiology, Anadolu University, Eskisehir, Turkey
Yusuf Öztürk
Affiliation:
Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Eskisehir, Turkey
*
Assistant Professor Dr Miris Dikmen, Faculty of Pharmacy, Department of Pharmacology, Anadolu University, Tepebasi TR-26470 Eskisehir, Turkey. Tel: +90 222 3350580/3748; Fax: +90 222 3350750; E-mail: mirisd@anadolu.edu.tr
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Extract

Dikmen M, Cantürk Z, Öztürk Y. Escitalopram oxalate, a selective serotonin reuptake inhibitor, exhibits cytotoxic and apoptotic effects in glioma C6 cells.

Objective: Various antidepressants, mainly tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), have been reported to exhibit potent anticancer properties in different cancer cells. In this study, we evaluated the antiproliferative and apoptotic effects of escitalopram oxalate (25, 50, 100 and 200 µM) on rat C6 glioma cells.

Methods: Cell proliferations were measured by [3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide] (MTT) assay, apoptosis was observed by flow cytometric analysis on C6 cells.

Results: Significant decreases in the proliferation of C6 glioma cells were detected depending on increases in the escitalopram concentrations and incubation periods. When compared to controls, C6 cell proliferations after 24 h incubation were determined with 97.7, 85.9, 74.5 and 67.9% for 25, 50, 100 and 200 µM escitalopram, respectively, while the cell proliferations after 48 h were established as 96.5, 68.0, 50.7 and 39.9% for 25, 50, 100 and 200 µM concentrations, respectively. IC50 value of escitalopram was able to be calculated as 106.97 µM after 48 h. Based on Annexin V-propidium iodide (PI) binding capacity for 25, 50, 100 and 200 µM escitalopram, apoptotic effects were determined as 17.0, 22.3, 12.5 and 7.8%, respectively.

Conclusion: Based on our findings, escitalopram oxalate was observed to induce cytotoxic and apoptotic activities in C6 cells.

Keywords

C6 gliomaescitalopram oxalateflow cytometryNIH3T3
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 23 , Issue 4 , August 2011 , pp. 173 - 178
Copyright
Copyright © Cambridge University Press 2011

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References

1.Chang, SM, Prados, MD.Chemotherapy for gliomas. Curr Opin Oncol 1995;7:207–213.CrossRefGoogle ScholarPubMed
2.Newton, HB.Primary brain tumors, review of etiology, diagnosis and treatment. Am Fam Physician 1994;49: 787–797.Google ScholarPubMed
3.Lieberman, A.Depression in Parkinson's disease. Acta Neurol Scand 2006;113:1–8.CrossRefGoogle ScholarPubMed
4.Tutton, PJM, Barkla, DH.Influence of inhibitors of serotonin uptake on intestinal epithelium and colorectal carcinomas. Br J Cancer 1982;46:260–265.CrossRefGoogle ScholarPubMed
5.Tsuruo, T, Lida, H, Nojiri, M, Tsukagoshi, S, Sakurai, Y.Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine. J Pharmacobiodyn 1983;6:145–147.CrossRefGoogle ScholarPubMed
6.Sauter, C.Cytostatic activity of commonly used tricyclic antidepressants. Oncology 1989;46:155–157.CrossRefGoogle ScholarPubMed
7.Merry, S, Hamilton, TG, Flanigan, P, Freshney, RI, Kaye, SB.Circumvention of pleiotropic drug resistance in subcutaneous tumors in vivo with verapamil and clomipramine. Eur J Cancer 1991;27:31–34.CrossRefGoogle ScholarPubMed
8.Pommerenke, EW, Volm, M.Reversal of doxorubicin-resistance in solid tumors by clomipramine. In Vivo 1995;9:99–102.Google ScholarPubMed
9.Stafford, RS, MacDonald, EA, Finkelstein, SN.National patterns of medication treatment for depression. Prim Care Companion J Clin Psychiatry 2001;3:232–235.Google ScholarPubMed
10.Wyllie, AH.Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 1980;284:555–556.CrossRefGoogle ScholarPubMed
11.Thompson, CB.Apoptosis in the pathogenesis and treatment of disease. Science 1995;267:1456–1462.CrossRefGoogle ScholarPubMed
12.Chiou, SH, Chen, SJ, Peng, CH et al. Fluoxetine up-regulation expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived stem cell. Biochem Biophys Res Commun 2006;343: 391–400.CrossRefGoogle ScholarPubMed
13.Kolla, N, Wei, Z, Richardson, JS, Li, XM.Amitriptyline and fluoxetine protects PC12 cells from cell death induced by hydrogen peroxide. J Psychiatry Neurosci 2005;30:196–201.Google ScholarPubMed
14.Youdim, MBH, Bakhle, YS.Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness. Br J Pharmacol 2006;147:287–296.CrossRefGoogle ScholarPubMed
15.Murphy, DL, Mitchell, PB, Potter, WZ. Novel pharmacological approaches to the treatment of depression. In: Bloom, FE, Kupfer, DL, eds. Psychophamacology: the fourth generation of progress. New York: Raven Press, 1995: 1143–1153.Google Scholar
16.Naoi, M, Maruyama, W, Akao, Y, Yi, H, Yamaoka, Y.Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading to cell death or neuroprotection. J Neural Transm 2006;71:67–77.Google Scholar
17.Levkovitz, Y, Gil-Ad, I, Zeldich, E, Dayag, M, Weizman, A.Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci 2005;27:29–42.CrossRefGoogle ScholarPubMed
18.Abdul, M, Logothetis, CJ, Hoosein, NM.Growth inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines. J Urol 1995;154:247–250.CrossRefGoogle ScholarPubMed
19.Xia, Z, Bergstrand, A, DePierre, JW, Nassberger, L.The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol 1999;13:338–347.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
20.Serafeim, A, Holder, MJ, Grafton, G et al. Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells. Blood 2003;101: 3212–3219.CrossRefGoogle ScholarPubMed
21.Serafeim, A, Grafton, G, Chamba, A et al. 5-Hydroxytryptamine drives apoptosis in biopsylike Burkitt lymphoma cells: reversal by selective serotonin reuptake inhibitors. Blood 2002;99:2545–2553.CrossRefGoogle ScholarPubMed
22.Meredith, EJ, Holder, MJ, Chamba, A et al. The serotonin transporter (SLC6A4) is present in B-cell clones of diverse malignant origin: probing a potential antitumor target for psychotropics. FASEB J 2005;19:1187–1189.CrossRefGoogle ScholarPubMed
23.Fotakis, G, Timbrell, JA.In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006;160:171–177.CrossRefGoogle ScholarPubMed
24.Mosmann, T.Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.CrossRefGoogle ScholarPubMed
25.Belkaid, A, Copland, IB, Massillon, D, Annabi, B.Silencing of the human microsomal glucose-6-phosphate translocase induces glioblastoma cells death: potential new target for the anticancer curcumin. FEBS Lett 2006;580:3746–3752.CrossRefGoogle Scholar
26.Atsumi, T, Tonosaki, K, Fujisawa, S.Induction of early apoptosis and ROS-generation activity in human gingival fibroblasts (HGF) and human submandibular gland carcinoma (HSG) cells treated with curcumin. Arch Oral Biol 2006;51:913–921.CrossRefGoogle ScholarPubMed
27.Levkovitz, Y, Gil-Ad, I, Zeldich, E, Dayag, M, Weizman, A.Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines. J Mol Neurosci 2005;27:29–42.CrossRefGoogle ScholarPubMed
28.Arimochi, H, Morita, K.Characterization of cytotoxic actions of tricyclic antidepressants on human HT29 colon carcinoma cells. Eur J Pharmacol 2006;541:17–23.CrossRefGoogle ScholarPubMed
29.Volpe, DA, Ellison, CD, Parchment, RE, Grieshaber, CK, Faustino, PJ.Effects of amitriptyline and fluoxetine upon the in vitro proliferation of tumor cell lines. J Exp Ther Oncol 2003;3:169–184.CrossRefGoogle ScholarPubMed
30.Peer, D, Margalit, R.Fluoxetine and reversal of multidrug resistance. Cancer Lett 2006;237:180–187.CrossRefGoogle ScholarPubMed
31.Parker, KA, Pilkington, GJ.Apoptosis of human malignant glioma-derived cell cultures treated with clomipramine hydrochloride, as detected by Annexin-V assay. Radiol Oncol 2006;40:87–93.Google Scholar
32.Xia, Z, DePierre, JW, Nassberger, L.Modulation of apoptosis induced by tricyclic antidepressants in human peripheral lymphocytes. J Biochem Mol Toxicol 1998;12:115–123.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
33.Xia, Z, Lundgren, B, Bergstrand, A, DePierre, JW, Nässberger, L.Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L). Biochem Pharmacol 1999;57:1199–1208.CrossRefGoogle ScholarPubMed