Evaluation of cytotoxic effects of amitriptyline on cervical cancer cells

Document Type : Original Article

Authors

1 Member of Young Researchers and Elite Club, Faculty of Basic Sciences, Hamadan Branch, Islamic Azad University, Hamadan, Iran

2 Avicenna International College, Budapest, Hungary

3 Department of Biology, Faculty of Basic Sciences, Shahr-Rey Branch, Payame Noor University, Tehran,

Abstract

Background and Objective: Many studies have shown that antidepressants can have anticancer effects; however, the anti-cancer effects of the antidepressant amitriptyline on cervical cancer cells are unclear. Accordingly, the present study investigated the cytotoxic effects of amitriptyline on cervical cancer cells.
Materials and Methods: In this experimental-laboratory study, cervical cancer cells with SW480 cell line were divided into control (untreated) and groups treated with concentrations of 78.125, 156.25, 312.5, 625, 1250 and 2500 µg/ml of amitriptyline. Cells were measured by the MTT method 24 and 48 hours after treatment. Data was analyzed using one-way analysis of variance.
Results: Cervical cancer cell survival significantly reduced after treatment at concentrations of 78.125, 156.25, 312.5, 625, 1250 and 2500 µg/ml after 24 and 48 hours (P<0.001). IC50 was 1742 and 928 for 24 and 48 hours, respectively.
Conclusion: The findings of this study indicate that amitriptyline has cytotoxic effects on cervical cancer cells. The results of this study can be considered in the field of cervical cancer treatment.

Keywords


  1. Park SH, Kim M, Lee S, Jung W, Kim B. Therapeutic potential of natural products in treatment of cervical cancer: a review. Nutrients 2021;13(1):154.
  2. Di C, Xu D. Effect of concomitant administration of oxycontin and amitriptyline on patients with severe cancer pain and depression. Tropical Journal of Pharmaceutical Research 2019;18(1):129-34.
  3. Kopsky DJ, Keppel Hesselink JM. High doses of topical amitriptyline in neuropathic pain: two cases and literature review. Pain Practice 2012;12(2):148-53.
  4. Walker AJ, Card T, Bates TE, Muir K. Tricyclic antidepressants and the incidence of certain cancers: a study using the GPRD. British Journal of Cancer 2011;104(1):193-7.
  5. Guan J, Tanaka S, Kawakami K. Anticonvulsants or antidepressants in combination pharmacotherapy for treatment of neuropathic pain in cancer patients: a systematic review and meta-analysis. The Clinical Journal of Pain 2016;32(8):719-25.
  6. Jahchan NS, Dudley JT, Mazur PK, Flores N, Yang D, Palmerton A, et al. A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors. Cancer Discovery 2013;3(12):1364-77.
  7. Toh S, García Rodríguez LA, Hernández-Díaz S. Use of antidepressants and risk of lung cancer. Cancer Causes & Control 2007;18(10):1055-64.
  8. Sperling CD, Aalborg GL, Dehlendorff C, Friis S, Mørch LS, Kjaer SK. Use of antidepressants and endometrial-cancer risk: a nationwide nested case–control study. International Journal of Epidemiology 2021 Sep 22;dyab200.
  9. Cordero MD, Sánchez-Alcázar JA, Bautista-Ferrufino MR, Carmona-López MI, Illanes M, Ríos MJ, Garrido-Maraver J, Alcudia A, Navas P, de Miguel M. Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs. Anti-cancer Drugs 2010;21(10):932-44.
  10. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. American Journal of Hospice and Palliative Medicine 2012;29(3):177-82.
  11. Ventafridda V, Bonezzi C, Caraceni A, De Conno F, Guarise G, Ramella G, et al. Antidepressants for cancer pain and other painful syndromes with deafferentation component: comparison of amitriptyline and trazodone. The Italian Journal of Neurological Sciences 1987;8(6):579-87.
  12. Kulaksiz-Erkmen G, Dalmizrak O, Dincsoy-Tuna G, Dogan A, Ogus IH, Ozer N. Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-π) and alpha (GST-α). Journal of Enzyme Inhibition and Medicinal Chemistry 2013;28(1):131-6.
  13. Zhang Z, Du X, Zhao C, Cao B, Zhao Y, Mao X. The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma. Anti-cancer drugs. 2013;24(8):792-8.
  14. Cosgrove L, Shi L, Creasey DE. Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers’ financial associations with industry. PLoS One 2011;6(4):e18210.
  15. Harlow BL, Cramer DW. Self-reported use of antidepressants or benzodiazepine tranquilizers and risk of epithelial ovarian cancer: evidence from two combined case-control studies (Massachusetts, United States). Cancer Cause Control 1995; 6(2): 130–134.
  16. L’Espérance S, Frenette S, Dionne A, Dionne JY. Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Supportive Care in Cancer 2013;21(5):1461-74.
  17. Steingart AB, Cotterchio M. Do antidepressants cause, promote, or inhibit cancers?. Journal of Clinical Epidemiology 1995;48(11):1407-12.
  18. Kim SH, Lee MR, Lee KC, Lee JH, Kwon HC, Kim DC, et al. Use of antidepressants in patients with breast cancer taking tamoxifen. Journal of Breast Cancer 2010 ;13(4):325-36.
  19. Harlow BL, Cramer DW, Baron JA, Titus-Ernstoff L, Greenberg ER. Psychotropic medication use and risk of epithelial ovarian cancer. Cancer Epidemiology and Prevention Biomarkers 1998 ;7(8):697-702.
  20. Steingart AB, Cotterchio M. Do antidepressants cause, promote, or inhibit cancers?. Journal of Clinical Epidemiology 1995;48(11):1407-12.
  21. Park SH, Kim M, Lee S, Jung W, Kim B. Therapeutic potential of natural products in treatment of cervical cancer: a review. Nutrients 2021;13(1):154.
  22. Di C, Xu D. Effect of concomitant administration of oxycontin and amitriptyline on patients with severe cancer pain and depression. Tropical Journal of Pharmaceutical Research 2019;18(1):129-34.
  23. Guimarães YM, Godoy LR, Longatto-Filho A, Reis RD. Management of Early-Stage Cervical Cancer: A Literature Review. Cancers 2022;14(3):575.
  24. Buda A, Borghese M, Puppo A, Perotto S, Novelli A, Borghi C,et al. Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review. Cancers 2022;14(3):797.
  25. Gholamhoseyni Z, Ahmadi R, Hamidi Y. The Cytotoxic Effect of Metformin on Cervical Cancer (Hela) Cells in Comparison with Non-Cancerous Kidney Cells. Qom University of Medical Sciences Journal 2018; 12 (10) :9-15.
  26. Zhang Z, Du X, Zhao C, Cao B, Zhao Y, Mao X. The antidepressant amitriptyline shows potent therapeutic activity against multiple myeloma. Anti-cancer Drugs 2013;24(8):792-8.
  27. Ma S, Zheng X, Zheng T, Huang F, Jiang J, Luo H, et al. Amitriptyline influences the mechanical withdrawal threshold in bone cancer pain rats by regulating glutamate transporter GLAST. Molecular Pain 2019;15:1-12.
  28. Sunilkumar MM, Finni CG, Lijimol AS, Rajagopal MR. Health-Related Suffering and Palliative Care in Breast Cancer. Current Breast Cancer Reports 2021;13(4):241-6.
  29. Horsboel TA, Kjaer SK, Johansen C, Suppli NP, Ammitzbøll G, Frøding LP,et al. Increased risk for depression persists for years among women treated for gynecological cancers-a register-based cohort study with up to 19 years of follow-up. Gynecologic Oncology 2019;153(3):625-32.
  30. Cosgrove L, Shi L, Creasey DE. Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers’ financial associations with industry. PLoS One 2011;6(4):e18210.
  31. Harlow BL, Cramer DW. Self-reported use of antidepressants or benzodiazepine tranquilizers and risk of epithelial ovarian cancer: evidence from two combined case-control studies (Massachusetts, United States). Cancer Cause Control 1995; 6(2): 130–134.
  32. L’Espérance S, Frenette S, Dionne A, Dionne JY. Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Supportive Care in Cancer 2013;21(5):1461-74.
  33. Steingart AB, Cotterchio M. Do antidepressants cause, promote, or inhibit cancers?. Journal of Clinical Epidemiology 1995;48(11):1407-12.