TİYOKOLŞİKOSİD’İN A549 AKCİĞER KANSERİ HÜCRELERİNDEKİ ANTİPROLİFERATİF ETKİLERİNİN ARAŞTIRILMASI
Yıl 2025,
Cilt: 2 Sayı: 2, 61 - 66, 30.06.2025
Seher Atasever
,
Aylin Aydın
,
Rüstem Anıl Uğan
Öz
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.
Etik Beyan
Etik kurul onayına gerek bulunmamaktadır.
Destekleyen Kurum
Bu çalışma TÜBİTAK 2209A lisans katılımlı araştırma projesi tarafından desteklenmektedir.
Proje Numarası
1919B012406535
Teşekkür
Bu çalışma TÜBİTAK 2209A lisans katılımlı araştırma projesi tarafından desteklenmektedir. Bu çalışma Seher ATASEVER’in lisans bitirme tezidir.
Kaynakça
-
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
Yıl 2025,
Cilt: 2 Sayı: 2, 61 - 66, 30.06.2025
Seher Atasever
,
Aylin Aydın
,
Rüstem Anıl Uğan
Öz
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.
Etik Beyan
Ethics committee approval is not required
Destekleyen Kurum
Scientific and Technological Research Council of Turkey (TUBITAK) 2209A
Proje Numarası
1919B012406535
Teşekkür
I would like to thank the Scientific and Technological Research Council of Turkey (TÜBİTAK) for supporting my undergraduate thesis project.
Kaynakça
-
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