Centaurea lycaonica Boiss. & Heldr. Bitkisinin İnsan Servikal Kanser Hücre Hattında Sitotoksisitesinin MTT Testi ve xCELLigence Sistemi ile Değerlendirilmesi
Year 2025,
Volume: 28 Issue: 1, 47 - 52, 12.02.2025
Centaurea L. cinsine ait birçok tür, dünyanın çeşitli bölgelerinde endemik olarak varlığını sürdürmekte ve halk hekimliğinde kullanımlarıyla literatürde yerini almaktadır. Söz konusu cinse ait bazı türlerin servikal kanser hücre hattı üzerindeki sitotoksisitesi incelenmiştir. Bu çalışmada Türkiye’ye endemik ve hakkında yok denecek kadar az sayıda çalışma bulunan Centaurea lycaonica türünün kök kısmından hareketle, 24 saat maserasyon yöntemiyle hazırlanmış diklorometan (CRD) ve metanol (CRM) ekstrelerinin 48 saatlik maruziyette insan servikal kanser hücre hattındaki (HeLa) sitotoksik etkisinin araştırılması amaçlandı. Bitki ekstresinden hazırlanan farklı konsantrasyonların hücre canlılığına etkisi çalışma prensipleri farklı olan MTT ve xCELLigence GZHA sistemi kullanılarak araştırıldı ve IC50 değerleri belirlendi. Sonuç olarak, CRD ve CRM ekstrelerinin MTT bulguları, xCELLigence analiziyle tutarlı olup HeLa hücrelerinde sitotoksik etkiye sahip olduğu bulundu. C. lycaonica türünün kanser tedavisinde yeni bir doğal kaynak olarak değerlendirilebileceği düşünüldü. Bu çalışmanın, Türkiye’ye endemik birçok türün biyolojik aktivite ve etki mekanizmalarının aydınlatılmasını teşvik edeceği düşünülmektedir.
Hazırlanmış olan bu araştırma çalışması, TÜBİTAK 2209-A kapsamında 1919B012314005 kodu ile desteklenen bitirme projesinden üretilmiş olup katkılarından dolayı TÜBİTAK’a teşekkürlerimizi sunarız.
References
Artun, F. T., & Karagöz, A. (2021). Antiproliferative and apoptosis-inducing effects of the methanolic extract of Centaurea hermannii in human cervical cancer cell line. Biotechnic & Histochemistry, 96(1), 1-10. https://doi.org/10.1080/10520295.2020.1751288
Atmaca, H., Bozkurt, E., Kısım, A., & Uslu, R. (2016). Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines. Turkish Journal of Biochemistry, 41(6), 413-421. https://doi.org/10.1515/tjb-2016-0128
Ayad, R., & Akkal, S. (2019). Phytochemistry and biological activities of Algerian Centaurea and related genera. Studies in natural products chemistry, 63, 357-414. https://doi.org/10.1016/B978-0-12-817901-7.00012-5
Brown, A. J., & Trimble, C. L. (2012). New technologies for cervical cancer screening. Best practice & research Clinical obstetrics & gynaecology, 26(2), 233-242. https://doi.org/10.1016/j.bpobgyn.2011.11.001
Davis P.H. (1970). Flora of Turkey and the East Aegean Islands. Vol. 3; 548-625.
Delgado-Waldo, I., Contreras-Romero, C., Salazar-Aguilar, S., Pessoa, J., Mitre-Aguilar, I., García-Castillo, V.,
... & Jacobo-Herrera, N. J. (2023). A triple-drug combination induces apoptosis in cervical cancer-derived cell lines. Frontiers in Oncology, 13, 1106667. https://doi.org/10.3389/fonc.2023.1106667
Erol-Dayı, Ö., Pekmez, M., Bona, M., Aras Perk, A., Arda, N. (2011). Total phenolic contents, antioxidant activities cytotoxicity of three Centaurea species: C. calcitrapa subsp. calcitrapa, C. ptosimopappa C. spicata. Free Radicals and Antioxidants, 1(2), 31-36. https://doi.org/10.5530/ax.2011.2.7
Fattaheian-Dehkordi, S., Hojjatifard, R., Saeedi, M., & Khanavi, M. (2021). A review on antidiabetic activity of Centaurea spp.: A new approach for developing herbal remedies. Evidence-based complementary and alternative medicine, 2021. https://doi.org/10.1155/2021/5587938
Gras, A., Parada, M., Pellicer, J., Vallès, J., & Garnatje, T. (2022). Cancer and Traditional Plant Knowledge, an Interesting Field to Explore: Data from the Catalan Linguistic Area. Molecules, 27(13), 4070. https://doi.org/10.3390/molecules27134070
Huang, W., Gfeller, V., & Erb, M. (2018). Root volatiles in plant-plant interactions II: Root terpenes from Centaurea stoebe modify Taraxacum officinale root chemistry and root herbivore growth. bioRxiv, 441790. https://doi.org/10.1101/441790
Jabri, T., Imran, M., Aziz, A., Rao, K., Kawish, M., Irfan, M., ... & Shah, M. R. (2019). Design and synthesis of mixed micellar system for enhanced anticancer efficacy of Paclitaxel through its co-delivery with Naringin. Drug development and industrial pharmacy, 45(5), 703-714. https://doi.org/10.1080/03639045.2018.1550091
Keser, S., Keser, F., Turkoglu, İ., Kaygılı, O., ... & Turkoglu S. (2020). In Vitro Biological Evaluation and
Phytochemical Contents of Three Centaurea L. Species Growing from Eastern Anatolia in Turkey. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 23(1), 148-156. https://doi.org/10.18016/ksutarimdoga.vi.589279
Khammar, A., & Djeddi, S. (2012). Pharmacological and biological properties of some Centaurea species. Eur J Sci Res, 84(3), 398-416. http://www.europeanjournalofscientificresearch.com
Kısa, D., Çelik, A., & İmamoğlu, R. (2024). Assessment of Inhibitory Ability Against Medicinally Important Enzymes with Invitro and In Silico Studies: Phenolic Content of Endemic Centaurea cadmea subsp. pontica. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(1), 14-25.
https://doi.org/10.18016/ksutarimdoga.vi.1294720
Koc, S., Isgor, B. S., Isgor, Y. G., Shomali Moghaddam, N., & Yildirim, O. (2015). The potential medicinal value of plants from Asteraceae family with antioxidant defense enzymes as biological targets. Pharmaceutical biology, 53(5), 746-751. https://doi.org/10.3109/13880209.2014.942788
Lopes, D. C. D. X. P., de Oliveira, T. B., Viçosa, A. L., Valverde, S. S., & Júnior, E. R. (2021). Anti-inflammatory activity of the compositae family and its therapeutic potential. Planta Medica, 87(01/02), 71-100. https://doi.org/10.1055/a-1178-5158
Lu, X., Yang, F., Chen, D., Zhao, Q., Chen, D., Ping, H., & Xing, N. (2020). Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. International Journal of Biological Sciences, 16(7), 1121. https://doi.org/10.7150/ijbs.41686
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
Oberg, H. H., Peters, C., Kabelitz, D., & Wesch, D. (2020). Real-time cell analysis (RTCA) to measure killer cell activity against adherent tumor cells in vitro. In Methods in Enzymology (Vol. 631, pp. 429-441). Academic Press. https://doi.org/10.1016/bs.mie.2019.07.020
Rajaram, S., & Gupta, B. (2021). Screening for cervical cancer: Choices & dilemmas. Indian Journal of Medical Research, 154(2), 210-220. https://doi.org/10.4103/ijmr.IJMR_857_20
Saklani, A., & Kutty, S. K. (2008). Plant-derived compounds in clinical trials. Drug discovery today, 13(3-4), 161-171. https://doi.org/10.1016/j.drudis.2007.10.010
Shaikh, R., Daniel, A., & Lyng, F. M. (2023). Raman Spectroscopy for Early Detection of Cervical Cancer, a Global Women’s Health Issue-A Review. Molecules, 28(6), 2502. https://doi.org/10.3390/molecules28062502
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660
Wu, L., Cao, K., Ni, Z., Wang, S., Li, W., Liu, X., & Chen, Z. (2019). Rhein reverses doxorubicin resistance in SMMC‐7721 liver cancer cells by inhibiting energy metabolism and inducing mitochondrial permeability transition pore opening. Biofactors, 45(1), 85-96. https://doi.org/10.1002/biof.1462
Xu, J., Liu, D., Niu, H., Zhu, G., Xu, Y., Ye, D., ... & Zhang, Q. (2017). Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. Journal of Experimental & Clinical Cancer Research, 36, 1-14. https://doi.org/10.1186/s13046-016-0487-8
Yuan, C. H., Horng, C. T., Lee, C. F., Chiang, N. N., Tsai, F. J., Lu, C. C., ... & Chen, F. A. (2017). Epigallocatechin gallate sensitizes cisplatin‐resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. Environmental toxicology, 32(3), 845-855. https://doi.org/10.1002/tox.22284
Evaluation of Cytotoxicity of Centaurea lycaonica Boiss. & Heldr. Plant on Human Cervical Cancer Cell Line with MTT Test and xCELLigence System
Year 2025,
Volume: 28 Issue: 1, 47 - 52, 12.02.2025
Many species belonging to the genus Centaurea L. are endemic in various parts of the world and are used in folk medicine. The cytotoxicity of some species belonging to this genus on cervical cancer cell lines was investigated. In this study, it was aimed to investigate the cytotoxic effect of dichloromethane (CRD) and methanol (CRM) extracts prepared by 24 h maceration method on human cervical cancer cell line (HeLa) at 48 h exposure based on the root part of Centaurea lycaonica, which is endemic to Turkey and about which there are almost no studies. The effect of different concentrations of plant extracts on cell viability was investigated using MTT and xCELLigence RTCA systems, which have different working principles, and IC50 values were determined. As a result, MTT findings of CRD and CRM extracts were consistent with xCELLigence analysis and found to have a cytotoxic effect on HeLa cells. It was thought that C. lycaonica species could be evaluated as a new natural source in cancer treatment. It is thought that this study will encourage the elucidation of the biological activities and mechanisms of action of many species endemic to Turkey.
Artun, F. T., & Karagöz, A. (2021). Antiproliferative and apoptosis-inducing effects of the methanolic extract of Centaurea hermannii in human cervical cancer cell line. Biotechnic & Histochemistry, 96(1), 1-10. https://doi.org/10.1080/10520295.2020.1751288
Atmaca, H., Bozkurt, E., Kısım, A., & Uslu, R. (2016). Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines. Turkish Journal of Biochemistry, 41(6), 413-421. https://doi.org/10.1515/tjb-2016-0128
Ayad, R., & Akkal, S. (2019). Phytochemistry and biological activities of Algerian Centaurea and related genera. Studies in natural products chemistry, 63, 357-414. https://doi.org/10.1016/B978-0-12-817901-7.00012-5
Brown, A. J., & Trimble, C. L. (2012). New technologies for cervical cancer screening. Best practice & research Clinical obstetrics & gynaecology, 26(2), 233-242. https://doi.org/10.1016/j.bpobgyn.2011.11.001
Davis P.H. (1970). Flora of Turkey and the East Aegean Islands. Vol. 3; 548-625.
Delgado-Waldo, I., Contreras-Romero, C., Salazar-Aguilar, S., Pessoa, J., Mitre-Aguilar, I., García-Castillo, V.,
... & Jacobo-Herrera, N. J. (2023). A triple-drug combination induces apoptosis in cervical cancer-derived cell lines. Frontiers in Oncology, 13, 1106667. https://doi.org/10.3389/fonc.2023.1106667
Erol-Dayı, Ö., Pekmez, M., Bona, M., Aras Perk, A., Arda, N. (2011). Total phenolic contents, antioxidant activities cytotoxicity of three Centaurea species: C. calcitrapa subsp. calcitrapa, C. ptosimopappa C. spicata. Free Radicals and Antioxidants, 1(2), 31-36. https://doi.org/10.5530/ax.2011.2.7
Fattaheian-Dehkordi, S., Hojjatifard, R., Saeedi, M., & Khanavi, M. (2021). A review on antidiabetic activity of Centaurea spp.: A new approach for developing herbal remedies. Evidence-based complementary and alternative medicine, 2021. https://doi.org/10.1155/2021/5587938
Gras, A., Parada, M., Pellicer, J., Vallès, J., & Garnatje, T. (2022). Cancer and Traditional Plant Knowledge, an Interesting Field to Explore: Data from the Catalan Linguistic Area. Molecules, 27(13), 4070. https://doi.org/10.3390/molecules27134070
Huang, W., Gfeller, V., & Erb, M. (2018). Root volatiles in plant-plant interactions II: Root terpenes from Centaurea stoebe modify Taraxacum officinale root chemistry and root herbivore growth. bioRxiv, 441790. https://doi.org/10.1101/441790
Jabri, T., Imran, M., Aziz, A., Rao, K., Kawish, M., Irfan, M., ... & Shah, M. R. (2019). Design and synthesis of mixed micellar system for enhanced anticancer efficacy of Paclitaxel through its co-delivery with Naringin. Drug development and industrial pharmacy, 45(5), 703-714. https://doi.org/10.1080/03639045.2018.1550091
Keser, S., Keser, F., Turkoglu, İ., Kaygılı, O., ... & Turkoglu S. (2020). In Vitro Biological Evaluation and
Phytochemical Contents of Three Centaurea L. Species Growing from Eastern Anatolia in Turkey. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 23(1), 148-156. https://doi.org/10.18016/ksutarimdoga.vi.589279
Khammar, A., & Djeddi, S. (2012). Pharmacological and biological properties of some Centaurea species. Eur J Sci Res, 84(3), 398-416. http://www.europeanjournalofscientificresearch.com
Kısa, D., Çelik, A., & İmamoğlu, R. (2024). Assessment of Inhibitory Ability Against Medicinally Important Enzymes with Invitro and In Silico Studies: Phenolic Content of Endemic Centaurea cadmea subsp. pontica. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(1), 14-25.
https://doi.org/10.18016/ksutarimdoga.vi.1294720
Koc, S., Isgor, B. S., Isgor, Y. G., Shomali Moghaddam, N., & Yildirim, O. (2015). The potential medicinal value of plants from Asteraceae family with antioxidant defense enzymes as biological targets. Pharmaceutical biology, 53(5), 746-751. https://doi.org/10.3109/13880209.2014.942788
Lopes, D. C. D. X. P., de Oliveira, T. B., Viçosa, A. L., Valverde, S. S., & Júnior, E. R. (2021). Anti-inflammatory activity of the compositae family and its therapeutic potential. Planta Medica, 87(01/02), 71-100. https://doi.org/10.1055/a-1178-5158
Lu, X., Yang, F., Chen, D., Zhao, Q., Chen, D., Ping, H., & Xing, N. (2020). Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways. International Journal of Biological Sciences, 16(7), 1121. https://doi.org/10.7150/ijbs.41686
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
Oberg, H. H., Peters, C., Kabelitz, D., & Wesch, D. (2020). Real-time cell analysis (RTCA) to measure killer cell activity against adherent tumor cells in vitro. In Methods in Enzymology (Vol. 631, pp. 429-441). Academic Press. https://doi.org/10.1016/bs.mie.2019.07.020
Rajaram, S., & Gupta, B. (2021). Screening for cervical cancer: Choices & dilemmas. Indian Journal of Medical Research, 154(2), 210-220. https://doi.org/10.4103/ijmr.IJMR_857_20
Saklani, A., & Kutty, S. K. (2008). Plant-derived compounds in clinical trials. Drug discovery today, 13(3-4), 161-171. https://doi.org/10.1016/j.drudis.2007.10.010
Shaikh, R., Daniel, A., & Lyng, F. M. (2023). Raman Spectroscopy for Early Detection of Cervical Cancer, a Global Women’s Health Issue-A Review. Molecules, 28(6), 2502. https://doi.org/10.3390/molecules28062502
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249. https://doi.org/10.3322/caac.21660
Wu, L., Cao, K., Ni, Z., Wang, S., Li, W., Liu, X., & Chen, Z. (2019). Rhein reverses doxorubicin resistance in SMMC‐7721 liver cancer cells by inhibiting energy metabolism and inducing mitochondrial permeability transition pore opening. Biofactors, 45(1), 85-96. https://doi.org/10.1002/biof.1462
Xu, J., Liu, D., Niu, H., Zhu, G., Xu, Y., Ye, D., ... & Zhang, Q. (2017). Resveratrol reverses Doxorubicin resistance by inhibiting epithelial-mesenchymal transition (EMT) through modulating PTEN/Akt signaling pathway in gastric cancer. Journal of Experimental & Clinical Cancer Research, 36, 1-14. https://doi.org/10.1186/s13046-016-0487-8
Yuan, C. H., Horng, C. T., Lee, C. F., Chiang, N. N., Tsai, F. J., Lu, C. C., ... & Chen, F. A. (2017). Epigallocatechin gallate sensitizes cisplatin‐resistant oral cancer CAR cell apoptosis and autophagy through stimulating AKT/STAT3 pathway and suppressing multidrug resistance 1 signaling. Environmental toxicology, 32(3), 845-855. https://doi.org/10.1002/tox.22284
Karaboğa Arslan, A. K., Güngörenler, E., Paşayeva, L., Bozkurt, M., et al. (2025). Centaurea lycaonica Boiss. & Heldr. Bitkisinin İnsan Servikal Kanser Hücre Hattında Sitotoksisitesinin MTT Testi ve xCELLigence Sistemi ile Değerlendirilmesi. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 28(1), 47-52. https://doi.org/10.18016/ksutarimdoga.vi.1496499