Oral administration of fluoxetine alters the proliferation/apoptosis balance of lymphoma cells and up-regulates T cell immunity in tumor-bearing mice

European Journal of Pharmacology

Volumn 659, Issue 2-3, 2011, Pages 265-272

  Frick, Luciana Romina ^a,b   Rapanelli, Maximiliano ^b   Arcos, Maria Laura Barreiro ^a   Cremaschi, Graciela Alicia ^a   Genaro, Ana Maria ^a  

^a Centre de Estudios Farmacologicos y Botanicos   (Argentina)

^b Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

Author keywords

Antidepressant; Cancer; Fluoxetine; Immunity; Serotonin

Indexed keywords

CASPASE 3; CYCLIN B; CYCLIN D3; CYCLIN E; CYCLINE; FLUOXETINE; GAMMA INTERFERON; PROTEIN BAD; PROTEIN BCL 2; PROTEIN P15; PROTEIN P16; PROTEIN P17; PROTEIN P53; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CANCER INHIBITION; CD8+ T LYMPHOCYTE; CELL CYCLE; CELL CYCLE ARREST; CELL PROLIFERATION; CELLULAR IMMUNITY; CONTROLLED STUDY; FEMALE; LYMPHOMA; LYMPHOMA CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; TREATMENT OUTCOME; TUMOR GROWTH; TUMOR IMMUNITY;

ADMINISTRATION, ORAL; ANIMALS; APOPTOSIS; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; FLUOXETINE; GENE EXPRESSION REGULATION, NEOPLASTIC; LYMPHOMA; MICE; MICE, INBRED BALB C; PROGNOSIS; SEROTONIN UPTAKE INHIBITORS; T-LYMPHOCYTES; TUMOR MARKERS, BIOLOGICAL; UP-REGULATION;

EID: 79955940561     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2011.03.037     Document Type: Article

References (65)

1. Abdul, M., Logothetis, C.J., Hoosein, N.M., 1995. Growth-inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines. J. Urol. 154, 247-250.
2. Alvaro, T., Lejeune, M., García, J.F., Salvadó, M.T., López, C., Bosch, R., Jaén, J., Escrivá, P., Pons, L.E., 2008. Tumor-infiltrated immune response correlates with alterations in the apoptotic and cell cycle pathways in Hodgkin and Reed-Sternberg cells. Clin. Cancer Res. 14, 685-691.
3. Arimochi, H., Morita, K., 2006. Characterization of cytotoxic actions of tricyclic antidepressants on human HT29 colon carcinoma cells. Eur. J. Pharmacol. 541, 17-23.
4. Baur, A.S., Shaw, P., Burri, N., Delacrétaz, F., Bosman, F.T., Chaubert, P., 1999. Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas. Blood 94, 1773-1781. (Pubitemid 29411328)
5. Brandes, L.J., Arron, R.J., Bogdanovic, R.P., Tong, J., Zaborniak, C.L., Hogg, G.R., Warrington, R.C., Fang, W., LaBella, F.S., 1992. Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. Cancer Res. 52, 3796-3800.
6. Cheng, N., van de Wetering, C.I., Knudson, C.M., 2008. p27 deficiency cooperates with Bcl-2 but not Bax to promote T-cell lymphoma. PLoS One 3, e1911.
7. Coogan, P.F., Palmer, J.R., Strom, B.L., Rosenberg, L., 2005. Use of selective serotonin reuptake inhibitors and the risk of breast cancer. Am. J. Epidemiol. 162, 835-838.
8. Coogan, P.F., Strom, B.L., Rosenberg, L., 2009. Antidepressant use and colorectal cancer risk. Pharmacoepidemiol. Drug Saf. 18, 1111-1114.
9. Dredge, K., Marriott, J.B., Todryk, S.M., Dalgleish, A.G., 2002. Adjuvants and the promotion of Th1-type cytokines in tumour immunotherapy. Cancer Immunol. Immunother. 51, 521-531.
10. Dulawa, S.C., Holick, K.A., Gundersen, B., Hen, R., 2004. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29, 1321-1330. (Pubitemid 38780655)
11. Edgar, V.A., Genaro, A.M., Cremaschi, G., Sterin-Borda, L., 1998. Fluoxetine action on murine T-lymphocyte proliferation: participation of PKC activation and calcium mobilisation. Cell. Signal. 10, 721-726.
12. Edgar, V.A., Sterin-Borda, L., Cremaschi, G.A., Genaro, A.M., 1999. Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation. Eur. J. Pharmacol. 372, 65-73.
13. Eisen, J.N., Irwin, J., Quay, J., Livnat, S., 1989. The effect of antidepressants on immune function in mice. Biol. Psychiatry 26, 805-817. (Pubitemid 20016480)
14. el-Deiry, W.S., Harper, J.W., O'Connor, P.M., Velculescu, V.E., Canman, C.E., Jackman, J., Pietenpol, J.A., Burrell, M., Hill, D.E., Wang, Y., Wiman, K.G., Mercer, W.E., Kastan, M.B., Kohn, K.W., Elledge, S.J., Kinzler, K.W., Vogelstein, B., 1994. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 54, 1169-1174.
15. Fazzino, F., Urbina, M., Cedeño, N., Lima, L., 2009. Fluoxetine treatment to rats modifies serotonin transporter and cAMP in lymphocytes, CD4+ and CD8+ subpopulations and interleukins 2 and 4. Int. Immunopharmacol. 9, 463-467.
16. Foss, F.M., 2002. Immunologic mechanisms of antitumor activity. Semin. Oncol. 29, 5-11.
17. Frank, M.G., Hendricks, S.E., Johnson, D.R., Wieseler, J.L., Burke, W.J., 1999. Antidepressants augment natural killer cell activity: in vivo and in vitro. Neuropsychobiology 39, 18-24. (Pubitemid 29037760)
18. Frick, L.R., Palumbo, M.L., Zappia, M.P., Brocco, M.A., Cremaschi, G.A., Genaro, A.M., 2008. Inhibitory effect of fluoxetine on lymphoma growth through the modulation of antitumor T-cell response by serotonin-dependent and independent mechanisms. Biochem. Pharmacol. 75, 1817-1826.
19. Frick, L.R., Rapanelli, M., Cremaschi, G.A., Genaro, A.M., 2009. Fluoxetine directly counteracts the adverse effects of chronic stress on T cell immunity by compensatory and specific mechanisms. Brain Behav. Immun. 23, 36-40.
20. Gallardo, F., Esteller, M., Pujol, R.M., Costa, C., Estrach, T., Servitje, O., 2004. Methylation status of the p15, p16 and MGMT promoter genes in primary cutaneous T-cell lymphomas. Haematologica 89, 1401-1403. (Pubitemid 39540583)
21. García, J.F., Camacho, F.I., Morente, M., Fraga, M., Montalbán, C., Alvaro, T., Bellas, C., Castaño, A., Díez, A., Flores, T., Martin, C., Martinez, M.A., Mazorra, F., Menárguez, J., Mestre, M.J., Mollejo, M., Sáez, A.I., Sánchez, L., Piris, M.A., 2003. Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood 101, 681-689. (Pubitemid 36077593)
22. Geisen, C., Karsunky, H., Yücel, R., Möröy, T., 2003. Loss of p27(Kip1) cooperates with cyclin E in T-cell lymphomagenesis. Oncogene 22, 1724-1729. (Pubitemid 36408187)
23. Genaro, A.M., Edgar, V.A., Sterin-Borda, L., 2000. Differential effects of fluoxetine on murine B-cell proliferation depending on the biochemical pathways triggered by distinct mitogens. Biochem. Pharmacol. 60, 1279-1283.
24. Gombart, A.F., Morosetti, R., Miller, C.W., Said, J.W., Koeffler, H.P., 1995. Deletions of the cyclin-dependent kinase inhibitor genes p16INK4A and p15INK4B in non-Hodgkin's lymphomas. Blood 86, 1534-1539.
25. Gordon, J., Barnes, N.M., 2003. Lymphocytes transport serotonin and dopamine: agony or ecstasy? Trends Immunol. 24, 438-443.
26. Hosokawa, Y., Yang, M., Kaneko, S., Tanaka, M., Nakashima, K., 1995. Synergistic gene expressions of cyclin E, cdk2, cdk5 and E2F-1 during the prolactin-induced G1/S transition in rat Nb2 pre-T lymphoma cells. Biochem. Mol. Biol. Int. 37, 393-399.
27. Jia, L., Shang, Y.Y., Li, Y.Y., 2008. Effect of antidepressants on body weight, ethology and tumor growth of human pancreatic carcinoma xenografts in nude mice. World J. Gastroenterol. 14, 4377-4382.
28. Kanavaros, P., Bai, M., Stefanaki, K., Poussias, G., Rontogianni, D., Zioga, E., Gorgoulis, V., Agnantis, N.J., 2001. Immunohistochemical expression of the p53,mdm2, p21/Waf-1, Rb, p16, Ki67, cyclin D1, cyclin A and cyclin B1 proteins and apoptotic index in T-cell lymphomas. Histol. Histopathol. 16, 377-386.
29. Kang-Decker, N., Tong, C., Boussouar, F., Baker, D.J., Xu, W., Leontovich, A.A., Taylor, W.R., Brindle, P.K., van Deursen, J.M., 2004. Loss of CBP causes T cell lymphomagenesis in synergy with p27Kip1 insufficiency. Cancer Cell 5, 177-189. (Pubitemid 38283803)
30. Karsunky, H., Geisen, C., Schmidt, T., Haas, K., Zevnik, B., Gau, E., Möröy, T., 1999. Oncogenic potential of cyclin E in T-cell lymphomagenesis in transgenic mice: evidence for cooperation between cyclin E and Ras but not Myc. Oncogene 18, 7816-7824. (Pubitemid 30061353)
31. Kinjo, T., Kowalczyk, P., Kowalczyk, M., Walaszek, Z., Nishimaki, T., Slaga, T.J., Hanausek, M., 2009. Desipramine inhibits the growth of a mouse skin squamous cell carcinoma cell line and affects glucocorticoid receptor-mediated transcription. Mol. Carcinog. 48, 1123-1130.
32. Knutson, K.L., Disis, M.L., 2005. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol. Immunother. 54, 721-728.
33. Krawczyk, C.M., Verstovsek, S., Ujházy, P., Maccubbin, D., Ehrke, M.J., 1995. Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice. Cancer Immunol. Immunother. 40, 347-357.
34. Kubera, M., Basta-Kaim, A., Skowron-Cendrzak, A., Mazur-Kolecka, B., Roman, A., Borycz, J., 1995. Effect of repeated amitriptyline administration to mice on the T lymphocyte proliferative activity and natural killer cell cytotoxicity. Pol. J. Pharmacol. 47, 321-326.
35. Kubera, M., Simbirtsev, A., Mathison, R., Maes, M., 2000. Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice. Psychiatry Res. 96, 255-266.
36. Kubera, M., Lin, A.H., Kenis, G., Bosmans, E., van Bockstaele, D., Maes, M., 2001. Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J. Clin. Psychopharmacol. 21, 199-206.
37. Kubera, M., Grygier, B., Arteta, B., Urbańska, K., Basta-Kaim, A., Budziszewska, B., Leśkiewicz, M., Kołaczkowska, E., Maes, M., Szczepanik, M., Majewska, M., Lasoń, W., 2009a. Age-dependent stimulatory effect of desipramine and fluoxetine pretreatment on metastasis formation by B16F10melanoma inmale C57BL/6 mice. Pharmacol. Rep. 61, 1113-1126.
38. Kubera, M., Maes, M., Budziszewska, B., Basta-Kaim, A., Leśkiewicz, M., Grygier, B., Rogóz, Z., Lasoń, W., 2009b. Inhibitory effects of amantadine on the production of pro-inflammatory cytokines by stimulated in vitro human blood. Pharmacol. Rep. 61, 1105-1112.
39. Kvarnström, M., Jenmalm, M.C., Ekerfelt, C., 2004. Effect of cryopreservation on expression of Th1 and Th2 cytokines in blood mononuclear cells from patients with different cytokine profiles, analysed with three common assays: an overall decrease of interleukin-4. Cryobiology 49, 157-168. (Pubitemid 39194678)
40. Lawlor, D.A., Jüni, P., Ebrahim, S., Egger, M.J., 2003. Systematic review of the epidemiologic and trial evidence of an association between antidepressant medication and breast cancer. Clin. Epidemiol. 56, 155-163.
41. Levkovitz, Y., Gil-Ad, I., Zeldich, E., Dayag, M., Weizman, A., 2005. 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. 27, 29-42.
42. Maes, M., 2001. Theimmunoregulatory effects of antidepressants. Hum. Psychopharmacol. 16, 95-103.
43. Maes, M., Kenis, G., Kubera, M., De Baets, M., Steinbusch, H., Bosmans, E., 2005. The negative immunoregulatory effects of fluoxetine in relation to the cAMP-dependent PKA pathway. Int. Immunopharmacol. 5, 609-618.
44. Martins, C.P., Berns, A., 2002. Loss of p27(Kip1) but not p21(Cip1) decreases survival and synergizes with MYC in murine lymphomagenesis. EMBO J. 21, 3739-3748. (Pubitemid 34787047)
45. Mena, A., Ioannou, X.P., Van Kessel, A., Van Drunen Little-Van Den Hurk, S., Popowych, Y., Babiuk, L.A., Godson, D.L., 2002. Th1/Th2 biasing effects of vaccination in cattle as determined by real-time PCR. J. Immunol. Methods 263, 11-21. (Pubitemid 34495458)
46. Møller, M.B., Nielsen, O., Pedersen, N.T., 2001. Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features. Am. J. Clin. Pathol. 115, 404-412.
47. Møller, M.B., Nielsen, O., Pedersen, N.T., 2002. Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma. Histopathology 41, 322-330. (Pubitemid 35279029)
48. Morente, M.M., Piris, M.A., Abraira, V., Acevedo, A., Aguilera, B., Bellas, C., Fraga, M., Garcia-Del-Moral, R., Gomez-Marcos, F., Menarguez, J., Oliva, H., Sanchez-Beato, M., Montalban, C., 1997. Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression. Blood 90, 2429-2436. (Pubitemid 27392727)
49. Ostrand-Rosenberg, S., 2005. CD4+ T lymphocytes: a critical component of antitumor immunity. Cancer Invest. 23, 413-419. (Pubitemid 41324359)
50. Otsuki, T., Clark, H.M., Wellmann, A., Jaffe, E.S., Raffeld, M., 1995. Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas. Cancer Res. 55, 1436-1440.
51. Palumbo, M.L., Canzobre, M.C., Pascuan, C.G., Ríos, H., Wald, M., Genaro, A.M., 2010. Stress induced cognitive deficit is differentially modulated in BALB/c and C57Bl/6 mice: correlation with Th1/Th2 balance after stress exposure. J. Neuroimmunol. 218, 12-20.
52. Pellegrino, T.C., Bayer, B.M., 1998. Modulation of immune cell function following fluoxetine administration in rats. Pharmacol. Biochem. Behav. 59, 151-157.
53. Pellegrino, T.C., Bayer, B.M., 2000. Specific serotonin reuptake inhibitor-induced decreases in lymphocyte activity require endogenous serotonin release. Neuroimmunomodulation 8, 179-187. (Pubitemid 32225752)
54. Ramos-Payán, R., Aguilar-Medina, M., Estrada-Parra, S., González-Y-Merchand, J.A., Favila-Castillo, L., Monroy-Ostria, A., Estrada-Garcia, I.C., 2003. Quantification of cytokine gene expression using an economical real-time polymerase chain reaction method based on SYBR Green I. Scand. J. Immunol. 57, 439-445.
55. Rapanelli, M., Frick, L.R., Zanutto, B.S., 2011. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus. PLoS One 6, e14713.
56. Rook, A.H., Wood, G.S., Yoo, E.K., Elenitsas, R., Kao, D.M., Sherman, M.L., Witmer, W.K., Rockwell, K.A., Shane, R.B., Lessin, S.R., Vonderheid, E.C., 1999. Interleukin-12 therapy of cutaneous T-cell lymphoma induces lesion regression and cytotoxic T-cell responses. Blood 94, 902-908. (Pubitemid 29361820)
57. Serafeim, A., Holder, M.J., Grafton, G., Chamba, A., Drayson, M.T., Luon, Q.T., Bunce, C.M., Gregory, C.D., Barnes, N.M., Gordon, J., 2003. Selective serotonin reuptake inhibitors directly signal for apoptosis in biopsy-like Burkitt lymphoma cells. Blood 101, 3212-3219. (Pubitemid 36858017)
58. Spanova, A., Kovaru, H., Lisa, V., Lukasova, E., Rittich, B., 1997. Estimation of apoptosis in C6 glioma cells treated with antidepressants. Physiol. Res. 46, 161-164.
59. Steingart, A.B., Cotterchio, M., 1995. Do antidepressants cause, promote, or inhibit cancers? J. Clin. Epidemiol. 48, 1407-1412.
60. Teramoto, N., Pokrovskaja, K., Szekely, L., Polack, A., Yoshino, T., Akagi, T., Klein, G., 1999. Expression of cyclin D2 and D3 in lymphoid lesions. Int. J. Cancer 81, 543-850.
61. Xia, Z., Karlsson, H., DePierre, J.W., Nässberger, L., 1997. Tricyclic antidepressants induce apoptosis in human T lymphocytes. Int. J. Immunopharmacol. 19, 645-654.
62. Xia, Z., DePierre, J.W., Nässberger, L., 1998. Modulation of apoptosis induced by tricyclic antidepressants in human peripheral lymphocytes. J. Biochem. Mol. Toxicol. 12, 115-123.
63. Xia, Z., Bergstrand, A., DePierre, J.W., Nassberger, L., 1999. The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J. Biochem. Mol. Toxicol. 13, 338-347.
64. Xiao, L., Eneroth, P., 1996. Tricyclic antidepressants inhibit human natural killer cells. Toxicol. Appl. Pharmacol. 137, 157-162.
65. Zhang, C.L., Kamarashev, J., Qin, J.Z., Burg, G., Dummer, R., Döbbeling, U., 2003. Expression of apoptosis regulators in cutaneous T-cell lymphoma (CTCL) cells. J. Pathol. 200, 249-254. (Pubitemid 36748034)