Research Article
Year 2023,
Volume: 48 Issue: 1, 161 - 167, 31.03.2023
Abstract
Purpose: Colon cancer is among the most common causes of death among cancers, and in the treatment of colon cancer, adjuvant chemotherapy is applied mainly after curative surgery, to prevent recurrence and metastases after resection. In recent years, local anesthetics have received increasing attention in cancer research. This study aimed to investigate the proliferative and apoptotic effects of local anesthetics levobupivacaine and ropivacaine on SW480 colon cancer cells.
Materials and Methods: In the study, different concentrations and durations of levobupivacaine and ropivacaine were applied to the SW480 colon cancer cell line and their effect on proliferation was determined by MTT analysis. The TUNEL method was used to determine its apoptotic activity. The results were evaluated statistically.
Results: It was determined that levobupivacaine and ropivacaine decreased cell proliferation in SW480 colon cancer cells depending on dose and time. It was also observed to promote apoptosis in colon cancer cells.
Conclusion: According to the study data, it was determined that levobupivacaine and ropivacaine acted cytotoxic by activating apoptosis in SW480 colon cancer cells. It is thought that these data will lead to multidisciplinary studies to elucidate the antitumor effect mechanism of local anesthetics.
Keywords
References
- Labianca R, Beretta GD, Kildani B, Milesi L, Merlin F, Mosconi S et al. Colon cancer. Crit Rev Oncol Hematol. 2010;74:106-33.
- Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009;18:1688-94.
- Parki DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
- Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine. 2008;15:147-51.
- Dinić J, Efferth T, García-Sosa AT, Grahovac J, Padrón JM, Pajeva I et al. Repurposing old drugs to fight multidrug resistant cancers. Drug Resist Updat. 2020;52:100713.
- Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18:41-58.
- 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;9:e89563.
- Lirk P, Berger R. Hollmann MW, Fiegl H. Lidocaine time-and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro. Br J Anaesth. 2012;109:200-7.
- Li C, Gao S, Li X, Li C, Ma L. Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA. Oncol Res. 2018;26:209.
- Li T, Chen L, Zhao H, Wu L, Masters J, Han C et al. Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro. J Anesth. 2019;33:17-25.
- Wang W, Zhu M, Xu Z, Li W, Dong X, Chen Y et al. Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity. Biol Res. 2019;52:36.
- Yanagidate F, Strichartz GR. Local anesthetics. Handb Exp Pharmacol. 2007;(177):95-127..
- Jose C, Hebert-Chatelain E, Amoedo ND, Roche E, Obre E, Lacombe D et al. Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells. Redox Biol. 2018;18:33-42.
- Kwakye AK, Kampo S, Lv J, Ramzan MN, Richard SA, Falagán AA et al. Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway. BMC Res Notes. 2020;13:1-8.
- Gong X, Dan J, Li F, Wang L. Suppression of mitochondrial respiration with local anesthetic ropivacaine targets breast cancer cells. J Thorac Dis. 2018;10:2804.
- Piegeler T, Schläpfer M, Dull RO, Schwartz DE, Borgeat A, Minshall RD et al. Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase. Br J Anaesth. 2015;115:784-91.
- Zhu G, Zhang L, Dan J, Zhu Q. Differential effects and mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity. BMC Anesthesiol. 2020;20:126.
- Kamiloglu S, Sari G, Ozdal T, Capanoglu E. Guidelines for cell viability assays. Food Front. 2020;1:332-49.
- Onder GO, Sezer G, Ozdamar S, Yay A. Melatonin has an inhibitory effect on MCF‐7 and MDA‐MB‐231 human breast cancer cell lines by inducing autophagy and apoptosis. Fundam Clin Pharmacol. 2022;36:1038-56.
- Pucci C, Martinelli C, Ciofani G. Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedscience. 2019;13:961.
- Vahabi S, Eatemadi A. Effects of anesthetic and analgesic techniques on cancer metastasis. Biomed Pharmacother. 2017;87:1-7.
- Castelli V, Giordano A, Benedetti E, Ippoliti R, Varrassi G, Cimini A. Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells. J Cell Physiol. 2020;235:3474-84.
- Mao SH, Zhu CH, Nie Y, Yu J, Wang L. Levobupivacaine induces ferroptosis by miR-489-3p/SLC7A11 signaling in gastric cancer. Front Pharmacol. 2021;12:681338.
- Hansen TG. Ropivacaine: a pharmacological review. Expert Rev Neurother. 2004;4:781-91.
- Zhao L, Han S, Hou J, Shi W, Zhao Y, Chen Y. The local anesthetic ropivacaine suppresses progression of breast cancer by regulating miR-27b-3p/YAP axis. Aging (Albany NY). 2021;13:16341.
- Li R, Xiao C, Liu H, Huang Y, Dilger JP, Lin J. Effects of local anesthetics on breast cancer cell viability and migration. BMC Cancer. 2018;18:666.
- Yin D, Liu L, Shi Z, Zhang L, Yang Y. Ropivacaine inhibits cell proliferation, migration and invasion, whereas induces oxidative stress and cell apoptosis by circSCAF11/miR-145-5p axis in glioma. Cancer Manag Res. 2020;12:11145.
- Kang DK, Zhao LY, Wang HL. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines. Rev Bras Anestesiol. 2016;66:594-602.
- Siekmann W, Tina E, Koskela von Sydow A, Gupta A. Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines. Oncol Lett. 2019;18:395-401.
- Cai XY, Xia Y, Yang SH, Liu XZ, Shao ZW, Liu YL et al. Ropivacaine-and bupivacaine-induced death of rabbit annulus fibrosus cells in vitro: involvement of the mitochondrial apoptotic pathway. Osteoarthr Cartil. 2015;23:1763-75.
Year 2023,
Volume: 48 Issue: 1, 161 - 167, 31.03.2023
Abstract
Amaç: Kolon kanseri, kanserler arasında en yaygın ölüm nedenleri arasında yer almakta olup, kolon kanseri tedavisinde rezeksiyon sonrası nüks ve metastazları önlemek için ağırlıklı olarak küratif cerrahi sonrası adjuvan kemoterapi uygulanmaktadır. Son yıllarda, lokal anestezikler kanser araştırmalarında giderek artan bir ilgi görmektedir. Bu çalışmada lokal anesteziklerden levobupivacaine ve ropivacaine'in SW480 kolon kanseri hücreleri üzerine proliferatif ve apoptotik etkilerinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: Çalışmada, farklı konsantrasyonlarda ve sürelerde levobupivakain ve ropivakain, SW480 kolon kanseri hücre hattına uygulanarak MTT analizi ile proliferasyona etkisi belirlendi. Apoptotik etkinliğini belirlemek için ise TUNEL yöntemi kullanıldı. Sonuçlar istatistiksel olarak değerlendirildi.
Bulgular: Levobupivakain ve ropivakain’ in doz ve zamana bağlı olarak SW480 kolon kanseri hücrelerinde hücre proliferasyonunu azalttığı belirlendi. Aynı zamanda kolon kanseri hücrelerinde apoptozu teşvik ettiği gözlendi.
Sonuç: Çalışma verilerine göre, levobupivakain ve ropivakain’ in SW480 kolon kanseri hücrelerin de apoptozu aktive ederek sitotoksik etki gösterdiği tespit edildi. Bu verilerin lokal anesteziklerin antitümör etki mekanizmasını aydınlatmak için multidisipliner çalışmalara öncülük edeceği düşünülmektedir.
Keywords
References
- Labianca R, Beretta GD, Kildani B, Milesi L, Merlin F, Mosconi S et al. Colon cancer. Crit Rev Oncol Hematol. 2010;74:106-33.
- Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 2009;18:1688-94.
- Parki DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108.
- Park HJ, Kim MJ, Ha E, Chung JH. Apoptotic effect of hesperidin through caspase3 activation in human colon cancer cells, SNU-C4. Phytomedicine. 2008;15:147-51.
- Dinić J, Efferth T, García-Sosa AT, Grahovac J, Padrón JM, Pajeva I et al. Repurposing old drugs to fight multidrug resistant cancers. Drug Resist Updat. 2020;52:100713.
- Pushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18:41-58.
- 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;9:e89563.
- Lirk P, Berger R. Hollmann MW, Fiegl H. Lidocaine time-and dose-dependently demethylates deoxyribonucleic acid in breast cancer cell lines in vitro. Br J Anaesth. 2012;109:200-7.
- Li C, Gao S, Li X, Li C, Ma L. Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA. Oncol Res. 2018;26:209.
- Li T, Chen L, Zhao H, Wu L, Masters J, Han C et al. Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro. J Anesth. 2019;33:17-25.
- Wang W, Zhu M, Xu Z, Li W, Dong X, Chen Y et al. Ropivacaine promotes apoptosis of hepatocellular carcinoma cells through damaging mitochondria and activating caspase-3 activity. Biol Res. 2019;52:36.
- Yanagidate F, Strichartz GR. Local anesthetics. Handb Exp Pharmacol. 2007;(177):95-127..
- Jose C, Hebert-Chatelain E, Amoedo ND, Roche E, Obre E, Lacombe D et al. Redox mechanism of levobupivacaine cytostatic effect on human prostate cancer cells. Redox Biol. 2018;18:33-42.
- Kwakye AK, Kampo S, Lv J, Ramzan MN, Richard SA, Falagán AA et al. Levobupivacaine inhibits proliferation and promotes apoptosis of breast cancer cells by suppressing the PI3K/Akt/mTOR signalling pathway. BMC Res Notes. 2020;13:1-8.
- Gong X, Dan J, Li F, Wang L. Suppression of mitochondrial respiration with local anesthetic ropivacaine targets breast cancer cells. J Thorac Dis. 2018;10:2804.
- Piegeler T, Schläpfer M, Dull RO, Schwartz DE, Borgeat A, Minshall RD et al. Clinically relevant concentrations of lidocaine and ropivacaine inhibit TNFα-induced invasion of lung adenocarcinoma cells in vitro by blocking the activation of Akt and focal adhesion kinase. Br J Anaesth. 2015;115:784-91.
- Zhu G, Zhang L, Dan J, Zhu Q. Differential effects and mechanisms of local anesthetics on esophageal carcinoma cell migration, growth, survival and chemosensitivity. BMC Anesthesiol. 2020;20:126.
- Kamiloglu S, Sari G, Ozdal T, Capanoglu E. Guidelines for cell viability assays. Food Front. 2020;1:332-49.
- Onder GO, Sezer G, Ozdamar S, Yay A. Melatonin has an inhibitory effect on MCF‐7 and MDA‐MB‐231 human breast cancer cell lines by inducing autophagy and apoptosis. Fundam Clin Pharmacol. 2022;36:1038-56.
- Pucci C, Martinelli C, Ciofani G. Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedscience. 2019;13:961.
- Vahabi S, Eatemadi A. Effects of anesthetic and analgesic techniques on cancer metastasis. Biomed Pharmacother. 2017;87:1-7.
- Castelli V, Giordano A, Benedetti E, Ippoliti R, Varrassi G, Cimini A. Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells. J Cell Physiol. 2020;235:3474-84.
- Mao SH, Zhu CH, Nie Y, Yu J, Wang L. Levobupivacaine induces ferroptosis by miR-489-3p/SLC7A11 signaling in gastric cancer. Front Pharmacol. 2021;12:681338.
- Hansen TG. Ropivacaine: a pharmacological review. Expert Rev Neurother. 2004;4:781-91.
- Zhao L, Han S, Hou J, Shi W, Zhao Y, Chen Y. The local anesthetic ropivacaine suppresses progression of breast cancer by regulating miR-27b-3p/YAP axis. Aging (Albany NY). 2021;13:16341.
- Li R, Xiao C, Liu H, Huang Y, Dilger JP, Lin J. Effects of local anesthetics on breast cancer cell viability and migration. BMC Cancer. 2018;18:666.
- Yin D, Liu L, Shi Z, Zhang L, Yang Y. Ropivacaine inhibits cell proliferation, migration and invasion, whereas induces oxidative stress and cell apoptosis by circSCAF11/miR-145-5p axis in glioma. Cancer Manag Res. 2020;12:11145.
- Kang DK, Zhao LY, Wang HL. Cytotoxic effects of local anesthesia through lidocaine/ropivacaine on human melanoma cell lines. Rev Bras Anestesiol. 2016;66:594-602.
- Siekmann W, Tina E, Koskela von Sydow A, Gupta A. Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines. Oncol Lett. 2019;18:395-401.
- Cai XY, Xia Y, Yang SH, Liu XZ, Shao ZW, Liu YL et al. Ropivacaine-and bupivacaine-induced death of rabbit annulus fibrosus cells in vitro: involvement of the mitochondrial apoptotic pathway. Osteoarthr Cartil. 2015;23:1763-75.
There are 30 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Clinical Sciences |
| Journal Section | Research |
| Authors | |
| Publication Date | March 31, 2023 |
| Acceptance Date | January 30, 2023 |
| Published in Issue | Year 2023 Volume: 48 Issue: 1 |
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