The anti-tumoral effects of different local anesthetics on human endometrial carcinoma cell line: An in-vitro study

Varlik Erel 1 * , Cigdem Yenisey 2
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1 Department of Anaesthesiology, Medical Faculty, Adnan Menderes University, Aydin, Turkey
2 Department of Clinic Biochemistry, Medical Faculty, Adnan Menderes University, Aydin, Turkey
* Corresponding Author
J CLIN MED KAZ, Volume 5, Issue 59, pp. 28-33. https://doi.org/10.23950/1812-2892-JCMK-00804
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ABSTRACT

Background: There is accumulating evidence on the inhibitory effect of local anesthetic agents on metastasis and tumor recurrence on various cancer types. In this study, we aimed to test the effects of lidocaine, bupivicaine and prilocaine on cellular viability and apoptosis on human endometrial adenocarcinoma cell lines (Ishikawa cells).
Material and methods: Human Endometrial adenocarcinoma cells (Ishikawa cells) were exposed to different concentrations of local anesthetic agents for 24, 48, and 72 hours. The cell viability assay was performed via MTT and concentrations corresponding to 50% effective concentration (EC50) of cells were determined for each agent. Apoptosis was evaluated via commercial Biocolor ApoPercentage assay.
Results: All of the three local anesthetics reduced the amount of viable tumor cells in a dose-dependent manner. The EC50 values (mM) at 24, 48 and 72 h incubation periods were 11.67, 1.915, 2.114 for lidocaine 11.4, 5.21, 3.12 for bupivacaine 7.64 mM, 7.3 mM, and 2.83 mM, for prilocaine respectively.
Conclusion: Lidocaine, bupivacaine, and prilocaine have anti-tumoral effects on Ishikawa cell lines. All of the tested agents induced apoptosis and necrosis at high concentrations in a dose dependent-manner.

CITATION

Erel V, Yenisey C. The anti-tumoral effects of different local anesthetics on human endometrial carcinoma cell line: An in-vitro study. J Clin Med Kaz. 2020;5(59):28-33. https://doi.org/10.23950/1812-2892-JCMK-00804

REFERENCES

  • Johnson SM, Saint John BE, Dine AP. Local anesthetics as antimicrobial agents: a review. Surg Infect (Larchmt). 2008; 9:205-13. https://doi.org/10.1089/sur.2007.036
  • Borgeat A, Aguirre J. Update on local anesthetics. Curr Opin. Anaesthesiol. 2010; 23:466-71. https://doi.org/10.1097/ACO.0b013e328339eef2
  • Cummings, K. C. 3rd, Xu, F., Cummings, L. C. & Cooper, G. S. A comparison of epidural analgesia and traditional pain management effects on survival and cancer recurrence after colectomy: a population-based study. Anesthesiology. 2012; 116:797-806. https://doi.org/10.1097/ALN.0b013e31824674f6
  • Exadaktylos, A. K., Buggy, D. J., Moriarty, D. C., Mascha, E. & Sessler, D. I. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006; 105:660-664.https://doi.org/10.1097/00000542-200610000-00008
  • Biki, B. et al. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology. 2008; 109:180-187. https://doi.org/10.1097/ALN.0b013e31817f5b73
  • Snyder, G. L. & Greenberg, S. Effect of anaesthetic technique and other perioperative factors on cancer recurrence. Brit. J. Anaesth. 2010; 105:106-115. https://doi.org/10.1093/bja/aeq164
  • Sakaguchi, Masahiro, Yoshihiro Kuroda, and Munetaka Hirose. "The Antiproliferative Effect of Lidocaine on Human Tongue Cancer Cells with Inhibition of the Activity of Epidermal Growth Factor Receptor. Anesthesia and Analgesia. 2006; 102:1103-7. https://doi.org/10.1213/01.ane.0000198330.84341.35
  • Tavare, Aniket N, Nicholas J. S. Perry, Laura L. Benzonana, Masao Takata, and Daqing Ma. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012; 1250:1237-50. https://doi.org/10.1002/ijc.26448
  • Jiang Y, Gou H, Zhu J, Tian S, Yu L. Lidocaine inhibits the invasion and migration of TRPV6-expressing cancer cells by TRPV6 downregulation. Oncologyb Letters. 2016; 12:1164-1170. https://doi.org/10.3892/ol.2016.4709
  • Chang YC, Liu CL, Chen MJ, Hsu YW, Chen SN, Lin CH, Chen CM, Yang FM, Hu MC. Local anesthetics induce apoptosis in human breast tumor cells. Anesth Analg. 2014; 118:116-24. https://doi.org/10.1213/ANE.0b013e3182a94479
  • Nakamura K, Kido H, Morimoto Y, Morimoto H, Kobayashi S, Morikawa M, Haneji T.Prilocaine induces apoptosis in osteoblastic cells. Can J Anaesth. 1999; 46:476-82. https://doi.org/10.1007/BF03012949
  • Werdehausen R, Fazeli S, Braun S, Hermanns H, Essmann F, Hollmann MW, Bauer I, Stevens MF. Apoptosis induction by different local anaesthetics in a neuroblastoma cell line. Br J Anaesth. 2009; 103:711-8. https://doi.org/10.1093/bja/aep236
  • Perez-Castro R, Patel S, Garavito-Aguilar ZV, Rosenberg A, Recio-Pinto E, Zhang J, Blanck TJ, Xu F. Cytotoxicity of local anesthetics in human neuronal cells. Anesth Analg. 2009; 108:997-1007. https://doi.org/10.1213/ane.0b013e31819385e1
  • Chang YC, Liu CL, Chen MJ, Hsu YW, Chen SN, Lin CH, Chen CM, Yang FM, Hu MC. Local anesthetics induce apoptosis in human breast tumor cells. Anesth Analg. 2014; 118:116-24. https://doi.org/10.1213/ANE.0b013e3182a94479
  • Xuan W, Zhao H, Hankin J, Chen L, Yao S, Ma D. Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro. Sci Rep. 2016; 19(6):262-77. https://doi.org/10.1038/srep26277
  • Mammoto T, Higashiyama S, Mukai M, Mammoto A, Ayaki M, Mashimo T, Hayashi Y, Kishi Y, Nakamura H, Akedo H. Infiltration anesthetic lidocaine inhibits cancer cell invasion by modulating ectodomain shedding of heparin-binding epidermal growth factor-like growth factor (HB-EGF). J Cell Physiol. 2002; 192:351-8. https://doi.org/10.1002/jcp.10145
  • Wang HW, Wang LY, Jiang L, Tian SM, Zhong TD, Fang XM. Amide-linked local anesthetics induce apoptosis in human non-small cell lung cancer. J Thorac Dis. 2016; 8:2748-2757. https://doi.org/10.21037/jtd.2016.09.66
  • Chang YC, Hsu YC, Liu CL, Huang SY, Hu MC, Cheng SP. Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway. PLoS One. 2014; 21:9. https://doi.org/10.1371/journal.pone.0089563
  • Kawasaki C, Kawasaki T, Ogata M, Sata T, Chaudry IH. Lidocaine enhances apoptosis and suppresses mitochondrial functions of human neutrophil in vitro. J Trauma. 2010; 68:401-8. https://doi.org/10.1097/TA.0b013e3181af6e56
  • Kamiya Y, Ohta K, Kaneko Y. Lidocaine-induced apoptosis and necrosis in U937 cells depending on its dosage. Biomed Res. 2005; 26:231-9. https://doi.org/10.2220/biomedres.26.231
  • Friederich P, Schmitz TP. Lidocaine-induced cell death in a human model of neuronal apoptosis. Eur J Anaesthesiol. 2002; 19:564-70. https://doi.org/10.1017/S0265021502000911
  • Werdehausen R, Braun S, Essmann F, Schulze-Osthoff K, Walczak H, Lipfert P, Stevens MF. Lidocaine induces apoptosis via the mitochondrial pathway independently of death receptor signaling. Anesthesiology. 2007; 107:136-43. https://doi.org/10.1097/01.anes.0000268389.39436.66
  • Lee HT, Xu H, Siegel CD, Krichevsky IE. Local anesthetics induce human renal cell apoptosis. Am J Nephrol. 2003; 23:129-39. https://doi.org/10.1159/000069304
  • Hirata M, Sakaguchi M, Mochida C, Sotozono C, Kageyama K, Kuroda Y, Hirose M. Lidocaine inhibits tyrosine kinase activity of the epidermal growth factor receptor and suppresses proliferation of corneal epithelial cells. Anesthesiology. 2004; 100:1206-10. https://doi.org/10.1097/00000542-200405000-00024