In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma
Yıl: 2018 Cilt: 42 Sayı: 5 Sayfa Aralığı: 414 - 421 Metin Dili: İngilizce DOI: 10.3906/biy-1802-11 İndeks Tarihi: 09-07-2020
In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma
Öz: Drug repurposing has been proved to be an effective strategy to meet the urgent need for novel anticancer agents for multiplemyeloma (MM) treatment. In this work, we aimed to investigate the anticancer effect and mechanism of tricyclic antidepressantnortriptyline (NTP) on the U266 MM cell line. The in vitro inhibitory effect of NTP at various doses and time points was studied.The combination potential of cisplatin-NTP was also investigated. Cell cycle analysis and three flow cytometric apoptosis assays wereperformed. NTP showed dose- and time-dependent inhibitory effects on the U266 MM cell line. NTP had greater inhibitory effectthan cisplatin ($IC_{50}$ 26 µM vs. 40 µM). The cisplatin-NTP combination is antagonistic. In addition to G2/M phase cell cycle arrest,NTP induced apoptosis as indicated by mitochondrial membrane potential and caspase-3 and annexin V assays. NTP has inhibitoryand apoptotic effects on U266 MM cells. The cisplatin-NTP combination indicated strong antagonism, which may have significantclinical relevance since antidepressants are commonly employed in adjuvant therapy for cancer patients. Based on these findings, thetherapeutic potential of NTP for MM treatment should be investigated with in-depth mechanistic studies and in vivo experiments.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Bilir A, Erguven M, Oktem G, Ozdemir A, Uslu A, Aktas E, Bonavinda B (2008). Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma. Int J Oncol 32: 829- 839.
- Bilir A, Erguven M, Yazihan N, Aktas E, Oktem G, Sabanci A (2010). Enhancement of vinorelbine-induced cytotoxicity and apoptosis by clomipramine and lithium chloride in human neuroblastoma cancer cell line SH-SY5Y. J Neurooncol 100: 385-395.
- Chou TC (2006). Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 58: 621-681.
- Desmarais JE, Looper KJ (2009). Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. J Clin Psychiatry 70: 1688-1697.
- DiPaola RS (2002). To arrest or not to G 2-M cell-cycle arrest. Clin Cancer Res 8: 3311-3314.
- Frick LR, Rapanelli M (2013). Antidepressants: Influence on cancer and immunity? Life Sci 92: 525-532.
- Hall MD, Okabe M, Shen DW, Liang XJ, Gottesman MM (2008). The role of cellular accumulation in determining sensitivity to platinum-based chemotherapy. Annu Rev Pharmacol Toxicol 48: 495-535.
- Heim M, Scharifi M, Zisowsky J, Jaehde U, Voliotis D, Seeber S, Strumberg D (2005). The Raf kinase inhibitor BAY 43- 9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell lines. Anticancer Drugs 16: 129-136.
- Hsu SS, Huang CJ, Chen JS, Cheng HH, Chang HT, Jiann BP, Lin KL, Wang JL, Ho CM, Jan CR (2004). Effect of nortriptyline on intracellular Ca2+ handling and proliferation in human osteosarcoma cells. Basic Clin Pharmacol Toxicol 95: 124-130.
- Jeon SH, Kim SH, Kim Y, Kim YS, Lim Y, Lee YH, Shin SY (2011). The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG glioma cells. Biochem Biophys Res Commun 413: 311-317.
- Kabolizadeh P, Engelmann BJ, Pullen N, Stewart JK, Ryan JJ, Farrell NP (2012). Platinum anticancer agents and antidepressants: desipramine enhances platinum-based cytotoxicity in human colon cancer cells. J Biol Inorg Chem 17: 123-132.
- Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 340: c693.
- Kinjo T, Kowalczyk P, Kowalczyk M, Walaszek Z, Nishimaki T, Slaga TJ, 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.
- Koepsell H, Lips K, Volk C (2007). Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 24: 1227-1251.
- Mao X, Hou T, Cao B, Wang W, Li Z, Chen S, Fei M, Hurren R, Gronda M, Wu D et al. (2011). The tricyclic antidepressant amitriptyline inhibits D-cyclin transactivation and induces myeloma cell apoptosis by inhibiting histone deacetylases: in vitro and in silico evidence. Mol Pharmacol 79: 672-680.
- Mimura N, Hideshima T, Anderson KC (2015). Novel therapeutic strategies for multiple myeloma. Exp Hematol 43: 732-741.
- Pan CC, Shaw CF, Huang JK, Kuo CC, Kuo DH, Shieh P, Lu T, Chen WC, Ho CM, Jan CR (2010). Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells. Drug Dev Res 71: 323-330.
- Rajkumar SV (2014). Multiple myeloma: 2014 update on diagnosis, risk-stratification and management. Am J Hematol 89: 998- 1009.
- Röllig C, Knop S, Bornhauser M (2015). Multiple myeloma. Lancet 385: 2197-2208.
- Ruetz S, Fabbro D, Zimmermann J, Meyer T, Gray N (2003). Chemical and biological profile of dual Cdk1 and Cdk2 inhibitors. Curr Med Chem Anticancer Agents 3: 1-14.
- Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A (1997). JC-1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett 411: 77-82.
- Stepulak A, Rzeski W, Sifringer M, Brocke K, Gratopp A, Kupisz K, Turski L, Ikonomidou C (2008). Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells. Cancer Biol Ther 7: 1685-1693.
- Tsai CM, Chen JT, Stewart DJ, Chiu CH, Lai CL, Hsiao SY, Chen YM, Chang KT (2011). Antagonism between gefitinib and cisplatin in non-small cell lung cancer cells: why randomized trials failed? J Thorac Oncol 6: 559-568.
- Tsakalozou E, Eckman AM, Bae Y (2012). Combination effects of docetaxel and doxorubicin in hormone-refractory prostate cancer cells. Biochem Res Int 10: 832059.
- Yeragani VK, Roose S, Mallavarapu M, Radhakrishna RK, Pesce V (2002). Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate. Neuropsychobiology 46: 125-135.
- Yuan SY, Cheng CL, Ho HC, Wang SS, Chiu KY, Su CK, Ou YC, Lin CC (2015). Nortriptyline induces mitochondria and death receptor-mediated apoptosis in bladder cancer cells and inhibits bladder tumor growth in vivo. Eur J Pharmacol 761: 309-320.
- Zhang N, Dai L, Qi Y, Di W, Xia P (2013). Combination of FTY720 with cisplatin exhibits antagonistic effects in ovarian cancer cells: role of autophagy. Int J Oncol 42: 2053-2059.
- Zhang Z, Du X, Zhao C, Cao B, Zhao Y, Mao X (2013). The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma. Anticancer Drugs 24: 792-798.
| APA | BİBER A, DURUSU İ, ÖZEN C (2018). In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. , 414 - 421. 10.3906/biy-1802-11 |
| Chicago | BİBER Ayşenur,DURUSU İpek Z.,ÖZEN Can In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. (2018): 414 - 421. 10.3906/biy-1802-11 |
| MLA | BİBER Ayşenur,DURUSU İpek Z.,ÖZEN Can In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. , 2018, ss.414 - 421. 10.3906/biy-1802-11 |
| AMA | BİBER A,DURUSU İ,ÖZEN C In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. . 2018; 414 - 421. 10.3906/biy-1802-11 |
| Vancouver | BİBER A,DURUSU İ,ÖZEN C In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. . 2018; 414 - 421. 10.3906/biy-1802-11 |
| IEEE | BİBER A,DURUSU İ,ÖZEN C "In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma." , ss.414 - 421, 2018. 10.3906/biy-1802-11 |
| ISNAD | BİBER, Ayşenur vd. "In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma". (2018), 414-421. https://doi.org/10.3906/biy-1802-11 |
| APA | BİBER A, DURUSU İ, ÖZEN C (2018). In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turkish Journal of Biology, 42(5), 414 - 421. 10.3906/biy-1802-11 |
| Chicago | BİBER Ayşenur,DURUSU İpek Z.,ÖZEN Can In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turkish Journal of Biology 42, no.5 (2018): 414 - 421. 10.3906/biy-1802-11 |
| MLA | BİBER Ayşenur,DURUSU İpek Z.,ÖZEN Can In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turkish Journal of Biology, vol.42, no.5, 2018, ss.414 - 421. 10.3906/biy-1802-11 |
| AMA | BİBER A,DURUSU İ,ÖZEN C In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turkish Journal of Biology. 2018; 42(5): 414 - 421. 10.3906/biy-1802-11 |
| Vancouver | BİBER A,DURUSU İ,ÖZEN C In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma. Turkish Journal of Biology. 2018; 42(5): 414 - 421. 10.3906/biy-1802-11 |
| IEEE | BİBER A,DURUSU İ,ÖZEN C "In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma." Turkish Journal of Biology, 42, ss.414 - 421, 2018. 10.3906/biy-1802-11 |
| ISNAD | BİBER, Ayşenur vd. "In vitro anticancer effect of tricyclic antidepressant nortriptyline on multiple myeloma". Turkish Journal of Biology 42/5 (2018), 414-421. https://doi.org/10.3906/biy-1802-11 |
