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TİYOKOLŞİKOSİD’İN A549 AKCİĞER KANSERİ HÜCRELERİNDEKİ ANTİPROLİFERATİF ETKİLERİNİN ARAŞTIRILMASI

Year 2025, Volume: 2 Issue: 2, 61 - 66, 30.06.2025
https://doi.org/10.62425/crihs.1703748

Abstract

Amaç: Bu çalışmanın amacı, Tiyokolşikosid'in A549 insan küçük hücreli dışı akciğer kanseri hücreleri üzerindeki IC₅₀ değerini MTT testi kullanarak belirlemek ve antiproliferatif ve yara iyileştirici etkilerini araştırmaktır.
Yöntem: Thiocolchicoside'ın A549 hücreleri üzerindeki sitotoksik ve yara iyileştirici etkileri in vitro olarak değerlendirildi. Hücre canlılığı, IC₅₀ değerlerini hesaplamak için MTT testi ile 24, 48 ve 72 saatlerde değerlendirildi. Ek olarak, hücre göçünü değerlendirmek için in vitro yara iyileşmesi (scratch) deneyi yapılmıştır.
Bulgular: Tiyokolşikosidin 24 saatteki IC₅₀ değeri 2,693×10-⁴ M olarak bulunmuştur. MTT test sonuçları yüksek konsantrasyonlarda önemli sitotoksisite gösterirken, daha düşük konsantrasyonların önemli bir etkisi olmamış veya hücre canlılığını artırmıştır. Sitotoksik etkiler zamanla artmış, 48 ve 72. saatlerde daha belirgin hale gelmiştir. Yara iyileşmesi deneylerinde, düşük Tiyokolşikosid konsantrasyonları yara kapanmasını önemli ölçüde arttırırken, yüksek konsantrasyonlar bu etkiyi azaltmıştır. İstatistiksel analiz, 24 saatteki en düşük konsantrasyon hariç, 24 ve 48 saatteki konsantrasyonlar arasında önemli farklılıklar olduğunu ortaya koymuştur.
Sonuç: Tiyokolşikosid, A549 hücreleri üzerinde doza ve zamana bağlı sitotoksik etkiler gösterir ve düşük konsantrasyonlarda yara iyileşmesini destekleyebilir, bu da kanser tedavisi ve doku onarımında potansiyel ikili rollere işaret eder.

Ethical Statement

Etik kurul onayına gerek bulunmamaktadır.

Supporting Institution

Bu çalışma TÜBİTAK 2209A lisans katılımlı araştırma projesi tarafından desteklenmektedir.

Project Number

1919B012406535

Thanks

Bu çalışma TÜBİTAK 2209A lisans katılımlı araştırma projesi tarafından desteklenmektedir. Bu çalışma Seher ATASEVER’in lisans bitirme tezidir.

References

  • Akhtar, N., & Bansal, J. G. (2017). Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer, 41(5), 328-339. https://doi.org/10.1016/j.currproblcancer.2017.07.002
  • Artusi, M., Santi, P., Colombo, P., & Junginger, H. (2003). Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies. International journal of pharmaceutics, 250(1), 203-213.
  • Balkrishna, A., Das, S. K., Pokhrel, S., Joshi, A., Laxmi, Verma, S., Sharma, V. K., Sharma, V., Sharma, N., & Joshi, C. (2019). Colchicine: Isolation, LC–MS QTof screening, and anticancer activity study of Gloriosa superba seeds. Molecules, 24(15), 2772.
  • Belani, C. P., Marts, S., Schiller, J., & Socinski, M. A. (2007). Women and lung cancer: epidemiology, tumor biology, and emerging trends in clinical research. Lung Cancer, 55(1), 15-23. https://doi.org/10.1016/j.lungcan.2006.09.008
  • Bhattacharya, S., Das, A., Datta, S., Ganguli, A., & Chakrabarti, G. (2016). Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy. Tumor Biology, 37, 10653-10664.
  • Brown, J. S., Amend, S. R., Austin, R. H., Gatenby, R. A., Hammarlund, E. U., & Pienta, K. J. (2023). Updating the Definition of Cancer. Mol Cancer Res, 21(11), 1142-1147. https://doi.org/10.1158/1541-7786.MCR-23-0411
  • Huang, C. X., Siwan, E., Fox, S. L., Longfield, M., Twigg, S. M., & Min, D. (2023). Comparison of digital and traditional skin wound closure assessment methods in mice. Laboratory Animal Research, 39(1), 25.
  • Kratzer, T. B., Bandi, P., Freedman, N. D., Smith, R. A., Travis, W. D., Jemal, A., & Siegel, R. L. (2024). Lung cancer statistics, 2023. Cancer, 130(8), 1330-1348. https://doi.org/10.1002/cncr.35128
  • Kurek, J. (2018). Cytotoxic colchicine alkaloids: from plants to drugs. Cytotoxicity, 6(45), 10.5772.
  • Lemjabbar-Alaoui, H., Hassan, O. U., Yang, Y. W., & Buchanan, P. (2015). Lung cancer: Biology and treatment options. Biochim Biophys Acta, 1856(2), 189-210. https://doi.org/10.1016/j.bbcan.2015.08.002
  • Lippi, G., & Mattiuzzi, C. (2019). Current Cancer Epidemiology. Journal of Epidemiology and Global Health, 9(4). https://doi.org/10.2991/jegh.k.191008.001
  • Mahendran, D., Selvam, K., Kumari, S., Venkateswara Swamy, K., Geetha, N., & Venkatachalam, P. (2020a). Thiocolchicoside and colchicine induced apoptosis in breast cancer (MCF-7) cells via up-regulated expression of p53 tumor suppressor protein gene: an in vitro and in silico docking approaches. Journal of Biologically Active Products from Nature, 10(4), 264-274.
  • Nobili, S., Lippi, D., Witort, E., Donnini, M., Bausi, L., Mini, E., & Capaccioli, S. (2009). Natural compounds for cancer treatment and prevention. Pharmacol Res, 59(6), 365-378. https://doi.org/10.1016/j.phrs.2009.01.017
  • Olofinsan, K., Abrahamse, H., & George, B. P. (2023). Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules, 28(14). https://doi.org/10.3390/molecules28145578
  • Reuter, S., Gupta, S. C., Phromnoi, K., & Aggarwal, B. B. (2012). Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug. Br J Pharmacol, 165(7), 2127-2139. https://doi.org/10.1111/j.1476-5381.2011.01702.x
  • Reuter, S., Prasad, S., Phromnoi, K., Ravindran, J., Sung, B., Yadav, V. R., Kannappan, R., Chaturvedi, M. M., & Aggarwal, B. B. (2010). Thiocolchicoside exhibits anticancer effects through downregulation of NF-kappaB pathway and its regulated gene products linked to inflammation and cancer. Cancer Prev Res (Phila), 3(11), 1462-1472. https://doi.org/10.1158/1940-6207.CAPR-10-0037
  • Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA Cancer J Clin, 73(1), 17-48. https://doi.org/10.3322/caac.21763
  • Sivakumar, G. (2013). Colchicine semisynthetics: chemotherapeutics for cancer? Current medicinal chemistry, 20(7), 892-898.
  • Wathoni, N., Puluhulawa, L. E., Joni, I. M., Muchtaridi, M., Mohammed, A. F. A., Elamin, K. M., Milanda, T., & Gozali, D. (2022). Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer. Drug Delivery, 29(1), 2959-2970

INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS

Year 2025, Volume: 2 Issue: 2, 61 - 66, 30.06.2025
https://doi.org/10.62425/crihs.1703748

Abstract

Objective: This study aims to determine the IC₅₀ value of Thiocolchicoside on A549 human non-small cell lung cancer cells using the MTT assay and to investigate its antiproliferative and wound healing effects.
Methods: The cytotoxic and wound healing effects of Thiocolchicoside on A549 cells were evaluated in vitro. Cell viability was assessed at 24, 48, and 72 hours by MTT assay to calculate IC₅₀ values. Additionally, an in vitro wound healing (scratch) assay was performed to evaluate cell migration.
Results: The IC₅₀ value of Thiocolchicoside at 24 hours was found to be 2.693×10⁻⁴ M. MTT assay results showed significant cytotoxicity at high concentrations, while lower concentrations had no significant effect or increased cell viability. Cytotoxic effects increased over time, being more evident at 48 and 72 hours. In wound healing assays, low concentrations of Thiocolchicoside significantly enhanced wound closure, whereas higher concentrations reduced this effect. Statistical analysis revealed significant differences between concentrations at 24 and 48 hours, except for the lowest concentration at 24 hours.
Conclusion: Thiocolchicoside exerts dose- and time-dependent cytotoxic effects on A549 cells and may promote wound healing at low concentrations, suggesting potential dual roles in cancer treatment and tissue repair.

Ethical Statement

Ethics committee approval is not required

Supporting Institution

Scientific and Technological Research Council of Turkey (TUBITAK) 2209A

Project Number

1919B012406535

Thanks

I would like to thank the Scientific and Technological Research Council of Turkey (TÜBİTAK) for supporting my undergraduate thesis project.

References

  • Akhtar, N., & Bansal, J. G. (2017). Risk factors of Lung Cancer in nonsmoker. Curr Probl Cancer, 41(5), 328-339. https://doi.org/10.1016/j.currproblcancer.2017.07.002
  • Artusi, M., Santi, P., Colombo, P., & Junginger, H. (2003). Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies. International journal of pharmaceutics, 250(1), 203-213.
  • Balkrishna, A., Das, S. K., Pokhrel, S., Joshi, A., Laxmi, Verma, S., Sharma, V. K., Sharma, V., Sharma, N., & Joshi, C. (2019). Colchicine: Isolation, LC–MS QTof screening, and anticancer activity study of Gloriosa superba seeds. Molecules, 24(15), 2772.
  • Belani, C. P., Marts, S., Schiller, J., & Socinski, M. A. (2007). Women and lung cancer: epidemiology, tumor biology, and emerging trends in clinical research. Lung Cancer, 55(1), 15-23. https://doi.org/10.1016/j.lungcan.2006.09.008
  • Bhattacharya, S., Das, A., Datta, S., Ganguli, A., & Chakrabarti, G. (2016). Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy. Tumor Biology, 37, 10653-10664.
  • Brown, J. S., Amend, S. R., Austin, R. H., Gatenby, R. A., Hammarlund, E. U., & Pienta, K. J. (2023). Updating the Definition of Cancer. Mol Cancer Res, 21(11), 1142-1147. https://doi.org/10.1158/1541-7786.MCR-23-0411
  • Huang, C. X., Siwan, E., Fox, S. L., Longfield, M., Twigg, S. M., & Min, D. (2023). Comparison of digital and traditional skin wound closure assessment methods in mice. Laboratory Animal Research, 39(1), 25.
  • Kratzer, T. B., Bandi, P., Freedman, N. D., Smith, R. A., Travis, W. D., Jemal, A., & Siegel, R. L. (2024). Lung cancer statistics, 2023. Cancer, 130(8), 1330-1348. https://doi.org/10.1002/cncr.35128
  • Kurek, J. (2018). Cytotoxic colchicine alkaloids: from plants to drugs. Cytotoxicity, 6(45), 10.5772.
  • Lemjabbar-Alaoui, H., Hassan, O. U., Yang, Y. W., & Buchanan, P. (2015). Lung cancer: Biology and treatment options. Biochim Biophys Acta, 1856(2), 189-210. https://doi.org/10.1016/j.bbcan.2015.08.002
  • Lippi, G., & Mattiuzzi, C. (2019). Current Cancer Epidemiology. Journal of Epidemiology and Global Health, 9(4). https://doi.org/10.2991/jegh.k.191008.001
  • Mahendran, D., Selvam, K., Kumari, S., Venkateswara Swamy, K., Geetha, N., & Venkatachalam, P. (2020a). Thiocolchicoside and colchicine induced apoptosis in breast cancer (MCF-7) cells via up-regulated expression of p53 tumor suppressor protein gene: an in vitro and in silico docking approaches. Journal of Biologically Active Products from Nature, 10(4), 264-274.
  • Nobili, S., Lippi, D., Witort, E., Donnini, M., Bausi, L., Mini, E., & Capaccioli, S. (2009). Natural compounds for cancer treatment and prevention. Pharmacol Res, 59(6), 365-378. https://doi.org/10.1016/j.phrs.2009.01.017
  • Olofinsan, K., Abrahamse, H., & George, B. P. (2023). Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules, 28(14). https://doi.org/10.3390/molecules28145578
  • Reuter, S., Gupta, S. C., Phromnoi, K., & Aggarwal, B. B. (2012). Thiocolchicoside suppresses osteoclastogenesis induced by RANKL and cancer cells through inhibition of inflammatory pathways: a new use for an old drug. Br J Pharmacol, 165(7), 2127-2139. https://doi.org/10.1111/j.1476-5381.2011.01702.x
  • Reuter, S., Prasad, S., Phromnoi, K., Ravindran, J., Sung, B., Yadav, V. R., Kannappan, R., Chaturvedi, M. M., & Aggarwal, B. B. (2010). Thiocolchicoside exhibits anticancer effects through downregulation of NF-kappaB pathway and its regulated gene products linked to inflammation and cancer. Cancer Prev Res (Phila), 3(11), 1462-1472. https://doi.org/10.1158/1940-6207.CAPR-10-0037
  • Siegel, R. L., Miller, K. D., Wagle, N. S., & Jemal, A. (2023). Cancer statistics, 2023. CA Cancer J Clin, 73(1), 17-48. https://doi.org/10.3322/caac.21763
  • Sivakumar, G. (2013). Colchicine semisynthetics: chemotherapeutics for cancer? Current medicinal chemistry, 20(7), 892-898.
  • Wathoni, N., Puluhulawa, L. E., Joni, I. M., Muchtaridi, M., Mohammed, A. F. A., Elamin, K. M., Milanda, T., & Gozali, D. (2022). Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer. Drug Delivery, 29(1), 2959-2970
There are 19 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Sciences, Basic Pharmacology, Medical Pharmacology
Journal Section Research Articles
Authors

Seher Atasever 0009-0006-8363-5512

Aylin Aydın 0009-0006-5793-5562

Rüstem Anıl Uğan 0000-0002-4837-2343

Project Number 1919B012406535
Publication Date June 30, 2025
Submission Date May 21, 2025
Acceptance Date June 26, 2025
Published in Issue Year 2025 Volume: 2 Issue: 2

Cite

APA Atasever, S., Aydın, A., & Uğan, R. A. (2025). INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS. Current Research in Health Sciences, 2(2), 61-66. https://doi.org/10.62425/crihs.1703748
AMA Atasever S, Aydın A, Uğan RA. INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS. Curr Res Health Sci. June 2025;2(2):61-66. doi:10.62425/crihs.1703748
Chicago Atasever, Seher, Aylin Aydın, and Rüstem Anıl Uğan. “INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS”. Current Research in Health Sciences 2, no. 2 (June 2025): 61-66. https://doi.org/10.62425/crihs.1703748.
EndNote Atasever S, Aydın A, Uğan RA (June 1, 2025) INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS. Current Research in Health Sciences 2 2 61–66.
IEEE S. Atasever, A. Aydın, and R. A. Uğan, “INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS”, Curr Res Health Sci, vol. 2, no. 2, pp. 61–66, 2025, doi: 10.62425/crihs.1703748.
ISNAD Atasever, Seher et al. “INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS”. Current Research in Health Sciences 2/2 (June2025), 61-66. https://doi.org/10.62425/crihs.1703748.
JAMA Atasever S, Aydın A, Uğan RA. INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS. Curr Res Health Sci. 2025;2:61–66.
MLA Atasever, Seher et al. “INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS”. Current Research in Health Sciences, vol. 2, no. 2, 2025, pp. 61-66, doi:10.62425/crihs.1703748.
Vancouver Atasever S, Aydın A, Uğan RA. INVESTIGATION OF THE ANTIPROLIFERATIVE EFFECTS OF THIOCOLCHICOSIDE ON A549 LUNG CANCER CELLS. Curr Res Health Sci. 2025;2(2):61-6.

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