Research Article
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In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline

Year 2024, Volume: 25 Issue: 1, 73 - 80, 15.04.2024
https://doi.org/10.23902/trkjnat.1356270

Abstract

Lung cancer is a type of cancer that is mostly diagnosed at an advanced stage and has a short survival time despite standard chemotherapy and targeted therapies. Terbutaline and Orci-prenaline are bronchodilator agents that are potent and selective β2 receptor agonists. The purpose of this study was to investigate to evaluate the effects of Terbutaline and Orci-prenaline on A549 human lung carcinoma cell line and Beas-2b human bronchial epithelial cell line. Cells were treated with 1, 10, 100, 200, 400 µM concentrations of Terbutaline and Orciprenaline. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and xCELLigence real-time cell analyzer were used to determine their effects on cell viability. The cell index was monitored continuously by visualizing the impedance of the E-plate wells. Because of the roles of Glycogen Synthase Kinase 3β (GSK3β) in a diverse range of cellular processes like metabolism, cell proliferation, differentiation and survival and its key position at several signaling pathways, GSK3β inhibition by Terbutaline and Orciprenaline was also investigated. The results showed that Terbutaline and Orciprenaline inhibits GSK-3β. The overall results led to the conclusion that Terbutaline and especially Orciprenaline may have potential therapeutic effects in lung carcinoma.

Ethical Statement

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

Supporting Institution

Erciyes University Scientific Research Projects Coordination Unit

Project Number

TLO-2022-12397 and TLO-2022-12398.

Thanks

I would like to thank Rukiye Aslan (Kayseri, Türkiye) for her help in the experiments.

References

  • 1. Alao, J.P., Stavropoulou, A.V., Lam, E.W., Charles Coombes, R. & Vigushin, D.M. 2006. Histone deacetylase inhibitor, trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells. Molecular cancer, 5: 1-11. https://doi.org/10.1186/1476-4598-5-8
  • 2. Barbaros, M.B. & Dikmen, M. 2015. Kanser immünoterapisi. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, 31(4): 177-182.
  • 3. Carter, J. L., Damjanovic, A. K., Molinaro, C. A., Vyas, S., Gridley, D. S., Thyagarajan, S., & Bellinger, D. L. 2006. Sympathetic modulation of mammalian prostate cancer in vitro. Brain, Behavior, and Immunity, 20(3): 8-9. https://doi.org/doi:10.1016/j.bbi.2006.04.016
  • 4. Chahl, L.A. & O'Donnell, S.R. 1968. The actions of orciprenaline and protokylol on guinea-pig trachea. British Journal of Pharmacology and Chemotherapy, 33(3): 552. https://doi.org/10.1111/j.1476-5381.1968.tb00504.x
  • 5. Cohen, P., Nimmo, H.G. & Proud, C.G. 1978. How does insulin stimulate glycogen synthesis? Biochemical Society Symposium, 43: 69-95.
  • 6. DeNicola, L.K., Gayle, M.O. & Blake, K.V. 2001. Drug therapy approaches in the treatment of acute severe asthma in hospitalised children. Paediatric Drugs, 3(7): 509-537. https://doi.org/10.2165/00128072-200103070-00003
  • 7. Horáková, K., Šovčı́ková, A., Seemannová, Z., Syrová, D., Bušányová, K., Drobná, Z. & Ferenčı́k, M. 2001. Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radical Biology and Medicine, 30(6): 650-664. https://doi.org/10.1016/S0891-5849(00)00508-6
  • 8. Inbar, S., Neeman, E., Avraham, R., Benish, M., Rosenne, E., & Ben-Eliyahu, S. 2011. Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity. PloS one, 6(4): e19246. https://doi.org/10.1371/journal.pone.0019246
  • 9. Li, J.S., Zhu, M., Tian, D., Wang, M.X., Wang, F., Li, N.P. & Wu, R.L. 2007. Glycogen synthase kinase 3beta induces cell cycle arrest in a cyclin D1-dependent manner in human lung adenocarcinoma cell line A549. Sheng li xue bao: Acta Physiologica Sinica, 59(2): 204-209.
  • 10. O’Flaherty, L., Shnyder, S.D., Cooper, P.A., Cross, S.J., Wakefield, J.G., Pardo, O.E. & Tavaré, J.M. 2019. Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer. PLoS One, 14(4): e0214610. https://doi.org/10.1371/journal.pone.0214610
  • 11. Parekh, P. & Rao, K.V.K. 2007. Overexpression of cyclin D1 is associated with elevated levels of MAP kinases, Akt and Pak1 during diethylnitrosamine‐induced progressive liver carcinogenesis. Cell Biology International, 31(1): 35-43. https://doi.org/10.1016/j.cellbi.2006.09.005
  • 12. Peng, C., Niu, R., Sun, Q., Cong, B., Zhao, Y., Guo, J. & Zhao, X. 2011. Effects of breathing booster training and inhalation of terbutaline and ambroxol aerosol on pulmonary function in postoperative lung cancer patients. Chinese Journal of Physical Medicine and Rehabilitation, 9: 697-700.
  • 13. Schabath, M.B. & Cote, M.L. 2019. Cancer progress and priorities: lung cancer. Cancer Epidemiology, Biomarkers & Prevention, 28(10): 1563-1579. https://doi.org/10.1158/1055-9965.EPI-19-0221
  • 14. Shakoori, A., Ougolkov, A., Yu, Z.W., Zhang, B., Modarressi, M.H., Billadeau, D.D. & Minamoto, T. 2005. Deregulated GSK3β activity in colorectal cancer: its association with tumor cell survival and proliferation. Biochemical and Biophysical Research Communications, 334(4): 1365-1373. https://doi.org/10.1016/j.bbrc.2005.07.041
  • 15. Sultan, K., Zamir, A., Ashraf, W., Imran, I., Saeed, H., Rehman, A.U. & Rasool, M. F. 2023. Clinical pharmacokinetics of terbutaline in humans: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology, 396(2): 213-227. https://doi.org/ 10.1007/s00210-022-02304-5
  • 16. Thapa, R., Gupta, G., Bhat, A.A., Almalki, W.H., Alzarea, S.I., Kazmi, I. & Dua, K. 2023. A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies. International Journal of Biological Macromolecules, 253(7): 127375. https://doi.org/10.1016/j.ijbiomac.2023.127375
  • 17. Urcan, E., Haertel, U., Styllou, M., Hickel, R., Scherthan, H. & Reichl, F.X. 2010. Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dental Materials, 26(1): 51-58. https://doi.org/10.1016/j.dental.2009.08.007
  • 18. Uzunhisarcıklı, E. Yerer, M.B. Neuroprotective Effects of Vapreotide on Tau Transfection–Induced Neurodegeneration. 2022. Neurotoxicity Research, 40(6): 1824-1837. https://doi.org/10.1007/s12640-022-00588-2
  • 19. Xu, Y., Wang, J., Wang, X., Zhou, X., Tang, J., Jie, X. & Wu, G. 2022. Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors. Cell Death Discovery, 8(1): 36. https://doi.org/10.1038/s41420-022-00818-8
  • 20. Zhou, K., Lai, Y., Wang, Y., Sun, X., Mo, C., Wang, J. & Che, G. 2020. Comprehensive pulmonary rehabilitation is an effective way for better postoperative outcomes in surgical lung cancer patients with risk factors: a propensity score-matched retrospective cohort study. Cancer Management and Research, 12: 8903. https://doi.org/10.2147/CMAR.S267322
Year 2024, Volume: 25 Issue: 1, 73 - 80, 15.04.2024
https://doi.org/10.23902/trkjnat.1356270

Abstract

Akciğer kanseri, çoğunlukla ileri evrede teşhis edilen ve standart kemoterapi ve hedefe yönelik tedavilere rağmen hayatta kalma süresi kısa olan bir kanser türüdür. Terbutalin ve Orsiprenalin, güçlü ve seçici β2 reseptör agonistleri olan bronkodilatör ajanlardır. Bu çalışmanın amacı, Terbutalin ve Orsiprenalin'in insan akciğer karsinom hücre hattı üzerindeki etkilerini sürekli izleme yoluyla araştırmaktır. Hücreler 1, 10, 100, 200, 400 µM konsantrasyonlarda Terbutalin/Orsiprenalin ile muamele edilmiştir. Bu bileşiklerin hücre canlılığı üzerindeki etkisini belirlemek için 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) testi ve xCELLigence gerçek zamanlı hücre analizörü kullanılmıştır. Hücre indeksi, E-plaka kuyularının empedansı görselleştirilerek sürekli olarak izlenmiştir. Glikojen Sentaz Kinaz 3β (GSK3β)'nın metabolizma, hücre çoğalması, farklılaşma ve hayatta kalma gibi çok çeşitli hücresel süreçlerdeki rolleri ve çeşitli sinyal yollarındaki kilit konumu nedeniyle, bu moleküllerin GSK3β inhibisyonu araştırılmıştır. Terbutalin ve Orsiprenalin'in GSK-3β'yı inhibe ettiği belirlenmiştir.

Project Number

TLO-2022-12397 and TLO-2022-12398.

References

  • 1. Alao, J.P., Stavropoulou, A.V., Lam, E.W., Charles Coombes, R. & Vigushin, D.M. 2006. Histone deacetylase inhibitor, trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells. Molecular cancer, 5: 1-11. https://doi.org/10.1186/1476-4598-5-8
  • 2. Barbaros, M.B. & Dikmen, M. 2015. Kanser immünoterapisi. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, 31(4): 177-182.
  • 3. Carter, J. L., Damjanovic, A. K., Molinaro, C. A., Vyas, S., Gridley, D. S., Thyagarajan, S., & Bellinger, D. L. 2006. Sympathetic modulation of mammalian prostate cancer in vitro. Brain, Behavior, and Immunity, 20(3): 8-9. https://doi.org/doi:10.1016/j.bbi.2006.04.016
  • 4. Chahl, L.A. & O'Donnell, S.R. 1968. The actions of orciprenaline and protokylol on guinea-pig trachea. British Journal of Pharmacology and Chemotherapy, 33(3): 552. https://doi.org/10.1111/j.1476-5381.1968.tb00504.x
  • 5. Cohen, P., Nimmo, H.G. & Proud, C.G. 1978. How does insulin stimulate glycogen synthesis? Biochemical Society Symposium, 43: 69-95.
  • 6. DeNicola, L.K., Gayle, M.O. & Blake, K.V. 2001. Drug therapy approaches in the treatment of acute severe asthma in hospitalised children. Paediatric Drugs, 3(7): 509-537. https://doi.org/10.2165/00128072-200103070-00003
  • 7. Horáková, K., Šovčı́ková, A., Seemannová, Z., Syrová, D., Bušányová, K., Drobná, Z. & Ferenčı́k, M. 2001. Detection of drug-induced, superoxide-mediated cell damage and its prevention by antioxidants. Free Radical Biology and Medicine, 30(6): 650-664. https://doi.org/10.1016/S0891-5849(00)00508-6
  • 8. Inbar, S., Neeman, E., Avraham, R., Benish, M., Rosenne, E., & Ben-Eliyahu, S. 2011. Do stress responses promote leukemia progression? An animal study suggesting a role for epinephrine and prostaglandin-E2 through reduced NK activity. PloS one, 6(4): e19246. https://doi.org/10.1371/journal.pone.0019246
  • 9. Li, J.S., Zhu, M., Tian, D., Wang, M.X., Wang, F., Li, N.P. & Wu, R.L. 2007. Glycogen synthase kinase 3beta induces cell cycle arrest in a cyclin D1-dependent manner in human lung adenocarcinoma cell line A549. Sheng li xue bao: Acta Physiologica Sinica, 59(2): 204-209.
  • 10. O’Flaherty, L., Shnyder, S.D., Cooper, P.A., Cross, S.J., Wakefield, J.G., Pardo, O.E. & Tavaré, J.M. 2019. Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer. PLoS One, 14(4): e0214610. https://doi.org/10.1371/journal.pone.0214610
  • 11. Parekh, P. & Rao, K.V.K. 2007. Overexpression of cyclin D1 is associated with elevated levels of MAP kinases, Akt and Pak1 during diethylnitrosamine‐induced progressive liver carcinogenesis. Cell Biology International, 31(1): 35-43. https://doi.org/10.1016/j.cellbi.2006.09.005
  • 12. Peng, C., Niu, R., Sun, Q., Cong, B., Zhao, Y., Guo, J. & Zhao, X. 2011. Effects of breathing booster training and inhalation of terbutaline and ambroxol aerosol on pulmonary function in postoperative lung cancer patients. Chinese Journal of Physical Medicine and Rehabilitation, 9: 697-700.
  • 13. Schabath, M.B. & Cote, M.L. 2019. Cancer progress and priorities: lung cancer. Cancer Epidemiology, Biomarkers & Prevention, 28(10): 1563-1579. https://doi.org/10.1158/1055-9965.EPI-19-0221
  • 14. Shakoori, A., Ougolkov, A., Yu, Z.W., Zhang, B., Modarressi, M.H., Billadeau, D.D. & Minamoto, T. 2005. Deregulated GSK3β activity in colorectal cancer: its association with tumor cell survival and proliferation. Biochemical and Biophysical Research Communications, 334(4): 1365-1373. https://doi.org/10.1016/j.bbrc.2005.07.041
  • 15. Sultan, K., Zamir, A., Ashraf, W., Imran, I., Saeed, H., Rehman, A.U. & Rasool, M. F. 2023. Clinical pharmacokinetics of terbutaline in humans: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology, 396(2): 213-227. https://doi.org/ 10.1007/s00210-022-02304-5
  • 16. Thapa, R., Gupta, G., Bhat, A.A., Almalki, W.H., Alzarea, S.I., Kazmi, I. & Dua, K. 2023. A review of Glycogen Synthase Kinase-3 (GSK3) inhibitors for cancers therapies. International Journal of Biological Macromolecules, 253(7): 127375. https://doi.org/10.1016/j.ijbiomac.2023.127375
  • 17. Urcan, E., Haertel, U., Styllou, M., Hickel, R., Scherthan, H. & Reichl, F.X. 2010. Real-time xCELLigence impedance analysis of the cytotoxicity of dental composite components on human gingival fibroblasts. Dental Materials, 26(1): 51-58. https://doi.org/10.1016/j.dental.2009.08.007
  • 18. Uzunhisarcıklı, E. Yerer, M.B. Neuroprotective Effects of Vapreotide on Tau Transfection–Induced Neurodegeneration. 2022. Neurotoxicity Research, 40(6): 1824-1837. https://doi.org/10.1007/s12640-022-00588-2
  • 19. Xu, Y., Wang, J., Wang, X., Zhou, X., Tang, J., Jie, X. & Wu, G. 2022. Targeting ADRB2 enhances sensitivity of non-small cell lung cancer to VEGFR2 tyrosine kinase inhibitors. Cell Death Discovery, 8(1): 36. https://doi.org/10.1038/s41420-022-00818-8
  • 20. Zhou, K., Lai, Y., Wang, Y., Sun, X., Mo, C., Wang, J. & Che, G. 2020. Comprehensive pulmonary rehabilitation is an effective way for better postoperative outcomes in surgical lung cancer patients with risk factors: a propensity score-matched retrospective cohort study. Cancer Management and Research, 12: 8903. https://doi.org/10.2147/CMAR.S267322
There are 20 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Research Article/Araştırma Makalesi
Authors

Ebru Uzunhisarcıklı 0000-0002-7088-7490

Project Number TLO-2022-12397 and TLO-2022-12398.
Early Pub Date March 11, 2024
Publication Date April 15, 2024
Submission Date September 6, 2023
Acceptance Date February 21, 2024
Published in Issue Year 2024 Volume: 25 Issue: 1

Cite

APA Uzunhisarcıklı, E. (2024). In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline. Trakya University Journal of Natural Sciences, 25(1), 73-80. https://doi.org/10.23902/trkjnat.1356270
AMA Uzunhisarcıklı E. In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline. Trakya Univ J Nat Sci. April 2024;25(1):73-80. doi:10.23902/trkjnat.1356270
Chicago Uzunhisarcıklı, Ebru. “In Vitro Evaluation of the Effects of Potential GSK-3β Inhibitors Terbutaline and Orciprenaline”. Trakya University Journal of Natural Sciences 25, no. 1 (April 2024): 73-80. https://doi.org/10.23902/trkjnat.1356270.
EndNote Uzunhisarcıklı E (April 1, 2024) In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline. Trakya University Journal of Natural Sciences 25 1 73–80.
IEEE E. Uzunhisarcıklı, “In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline”, Trakya Univ J Nat Sci, vol. 25, no. 1, pp. 73–80, 2024, doi: 10.23902/trkjnat.1356270.
ISNAD Uzunhisarcıklı, Ebru. “In Vitro Evaluation of the Effects of Potential GSK-3β Inhibitors Terbutaline and Orciprenaline”. Trakya University Journal of Natural Sciences 25/1 (April 2024), 73-80. https://doi.org/10.23902/trkjnat.1356270.
JAMA Uzunhisarcıklı E. In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline. Trakya Univ J Nat Sci. 2024;25:73–80.
MLA Uzunhisarcıklı, Ebru. “In Vitro Evaluation of the Effects of Potential GSK-3β Inhibitors Terbutaline and Orciprenaline”. Trakya University Journal of Natural Sciences, vol. 25, no. 1, 2024, pp. 73-80, doi:10.23902/trkjnat.1356270.
Vancouver Uzunhisarcıklı E. In vitro evaluation of the effects of potential GSK-3β inhibitors terbutaline and orciprenaline. Trakya Univ J Nat Sci. 2024;25(1):73-80.

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