Dittrichia viscosa Bitkisinin Farklı Hücre Hatlarında Antiproliferatif ve Antioksidan Etkilerinin Değerlendirilmesi

Öz

Amaç: Kanser, fizyolojik ve moleküler düzeyde meydana gelen bozukluklara bağlı olarak kontrolsüz hücre proliferasyonu ile karakterize edilen kompleks bir hastalık grubudur. Son yıllarda, çevre dostu ve toksisitesi düşük bitkisel kaynaklardan elde edilen antikanser bileşiklere yönelik ilgi artmıştır. Bu bağlamda, Asteraceae familyasına ait olan ve anti-enflamatuar, antimikrobiyal, antikanser ve antidiyabetik özellikleri ile bilinen Dittrichia viscosa bitkisinin farklı hücre hatları üzerindeki sitotoksik ve antioksidan potansiyelinin değerlendirilmesi amaçlanmıştır. Materyal ve Yöntem: Çalışmada D. viscosa bitkisinden metanol ve hekzan çözücüleri kullanılarak özütler elde edilmiştir. Bu özütler sekiz farklı konsantrasyonda hazırlanarak A549 (akciğer karsinomu), HEPG2 (karaciğer karsinomu), MCF-7 ve MDA-MB-231 (meme karsinomu) hücre hatları üzerine uygulanmıştır. Hücre canlılığı, MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür) testi ile analiz edilmiştir. Ayrıca, hekzan ekstraktının antioksidan aktivitesi DPPH (2,2-difenil-1-pikrilhidrazil) radikal süpürme yöntemi ile belirlenmiştir. Araştırma Bulguları Yapılan analizler sonucunda en yüksek sitotoksik etkinin A549 hücre hattında 100 μg/ml konsantrasyonunda uygulanan hekzan ekstraktı ile %54 oranında gerçekleştiği gözlemlenmiştir. Genel olarak, hekzan ekstraktının metanol ekstraktına kıyasla daha güçlü sitotoksik etki gösterdiği belirlenmiştir. DPPH analizlerinde metanol ve hekzan özütleri daha düşük düzeyde ve daha stabil antioksidan etki göstermiş olup, bu etkinin metanol ekstraktında hekzana göre bir miktar daha yüksek olduğu belirlenmiştir. Sonuçlar: D. viscosa bitkisinin özellikle hekzan ekstraktının bazı kanser hücre hatları üzerinde belirgin sitotoksik etki oluşturduğu görülmüştür. A549 ve MDA-MB-231 hücre hatlarında düşük konsantrasyonlarda dahi etkinliğin yüksek olması, bu bitkinin potansiyel antikanser ajanlar arasında değerlendirilebileceğini göstermektedir. Bununla birlikte, antioksidan aktivitenin sınırlı olduğu göz önünde bulundurulduğunda, bitkinin bu etkisi ile ilgili daha kapsamlı araştırmalara ihtiyaç duyulmaktadır

Anahtar Kelimeler

• Antioksidan
• Hücre hatları
• Sitotoksik aktivite
• Dittrichia viscosa
• MTT testi

Evaluation of Antiproliferative and Antioxidant effects of Dittrichia viscosa in Different Cell Lines

Abstract

Objective: Cancer is a complex group of diseases characterized by uncontrolled cell proliferation due to disorders at the physiological and molecular levels. In recent years, there has been an increased interest in anticancer compounds derived from environmentally friendly and low toxicity plant sources. In this context, it was aimed to evaluate the cytotoxic and antioxidant potential of Dittrichia viscosa, a plant belonging to the Asteraceae family and known for its anti-inflammatory, antimicrobial, anticancer and antidiabetic properties, on different cell lines. Materials and Methods: In this study, extracts were obtained from D. viscosa plant using methanol and hexane solvents. These extracts were prepared at eight different concentrations and applied on A549 (lung carcinoma), HEPG2 (liver carcinoma), MCF-7 and MDA-MB-231 (breast carcinoma) cell lines. Cell viability was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. In addition, the antioxidant activity of the hexane extract was determined by DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging method. Results: As a result of the analysis, it was observed that the highest cytotoxic effect was realized by 54% with hexane extract applied at a concentration of 100 μg/ml in A549 cell line. In general, the hexane extract showed a stronger cytotoxic effect than the methanol extract. In DPPH assays, methanol and hexane extracts showed lower and more stable antioxidant effect and this effect was slightly higher in methanol extract than hexane. Conclusion: It was observed that especially the hexane extract of D. viscosa had a significant cytotoxic effect on some cancer cell lines. The high activity even at low concentrations in A549 and MDA-MB-231 cell lines indicates that this plant can be evaluated among potential anticancer agents. However, given the limited antioxidant activity, more extensive research on this effect of the plant is needed.

Keywords

• Antioxidant
• Cell lines
• Cytotoxic activity
• Dittrichia viscosa
• MTT assay

References

1. Alkaraki, A., Alshaer, W., Wehaibi, S., Gharaibeh, L., Abuarqoub, D., Alqudah, D. A., Al-Azzawi, H., Zureigat, H., Souleiman, M., & Awidi, A. (2020). Enhancing chemosensitivity of wild-type and drug-resistant MDA-MB-231 triple-negative breast cancer cell line to doxorubicin by silencing of STAT 3, Notch-1, and β-catenin genes. Breast Cancer, 27(5), 989–998. https://doi.org/10.1007/s12282-020-01098-9
2. Arzumanian, V. A., Kiseleva, O. I., & Poverennaya, E. V. (2021). The Curious Case of the HepG2 Cell Line: 40 Years of Expertise. International Journal of Molecular Sciences, 22(23), Article 23. https://doi.org/10.3390/ijms222313135
3. Asraoui, F., Kounnoun, A., Cacciola, F., El Mansouri, F., Kabach, I., Oulad El Majdoub, Y., Alibrando, F., Arena, K., Trovato, E., Mondello, L., & Louajri, A. (2021). Phytochemical Profile, Antioxidant Capacity, α-Amylase and α-Glucosidase Inhibitory Potential of Wild Moroccan Inula viscosa (L.) Aiton Leaves. Molecules, 26(11), Article 11. https://doi.org/10.3390/molecules26113134
4. Ayyoub, S., Al-Trad, B., Aljabali, A. A. A., Alshaer, W., Al Zoubi, M., Omari, S., Fayyad, D., & Tambuwala, M. M. (2022). Biosynthesis of gold nanoparticles using leaf extract of Dittrichia viscosa and in vivo assessment of its anti-diabetic efficacy. Drug Delivery and Translational Research, 12(12), 2993–2999. https://doi.org/10.1007/s13346-022-01163-0
5. Bar-Shalom, R., Bergman, M., Grossman, S., Azzam, N., Sharvit, L., & Fares, F. (2019). Inula Viscosa Extract Inhibits Growth of Colorectal Cancer Cells in vitro and in vivo Through Induction of Apoptosis. Frontiers in Oncology, 9, 227. https://doi.org/ 10.3389/fonc.2019.00227
6. Brahmi, N., Scognamiglio, M., Pacifico, S., Mekhoukhe, A., Madani, K., Fiorentino, A., & Monaco, P. (2015). 1H NMR based metabolic profiling of eleven Algerian aromatic plants and evaluation of their antioxidant and cytotoxic properties. Food Research International, 76, 334–341. https://doi.org /10.1016/j.foodres.2015.07.005
7. Chen, B., Zou, H., Zhang, B., Zhang, X., Jin, X., Wang, C., & Zhang, X. (2022). Distribution pattern and change prediction of Saposhnikovia divaricata suitable area in China under climate change. Ecological Indicators, 143, 109311. https://doi.org/10.1016/ j.ecolind.2022.109311
8. Çolak, S., Çömlekcı̇oğlu, N., & Aygan, A. (2020). Urtica dioica Bitki Özütlerinin Antioksidan ve Antimikrobiyal Aktivitelerinin İncelenmesi. Eurasian Journal of Biological and Chemical Sciences, 3((Suppl 1)), Article (Suppl 1).

9. Dalkiliç, S., Dalkiliç, L. K., Fı̇dan, S., Tı̇murkaan, M., Uygur, L., Akay, G., & Korkmaz, İ. (2023). Mentha pulegium extracts showed strong antimicrobial and cytotoxic effects in vitro. Kahramanmaraş Sütçü İmam Üniversitesi Tarım ve Doğa Dergisi, 26(6), Article 6. https://doi.org/10.18016/ksutarimdoga.vi.1192081
10. Debela, D. T., Muzazu, S. G., Heraro, K. D., Ndalama, M. T., Mesele, B. W., Haile, D. C., Kitui, S. K., & Manyazewal, T. (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Medicine, 9, 20503121211034366. https://doi.org/ 10.1177/ 20503121211034366
11. Donato, M. T., Tolosa, L., & Gómez-Lechón, M. J. (2015). Culture and Functional Characterization of Human Hepatoma HepG2 Cells. In M. Vinken & V. Rogiers (Eds.), Protocols in In Vitro Hepatocyte Research (pp. 77–93). Springer. https://doi.org/10.1007/978-1-4939-2074-7_5
12. Grauso, L., Cesarano, G., Zotti, M., Ranesi, M., Sun, W., Bonanomi, G., & Lanzotti, V. (2020). Exploring Dittrichia viscosa (L.) Greuter phytochemical diversity to explain its antimicrobial, nematicidal and insecticidal activity. Phytochemistry Reviews, 19(3), 659–689. https://doi.org/10.1007/s11101-019-09607-1
13. Hamurcu, F. (2023). N-Benziletilendiamin Birimi İçeren Yeni Shiff Bazlarının Sentezi, Karakterizasyonu ve İnsan Kolon Kanseri Hücreleri Üzerine Sitotoksik Etkilerinin Belirlenmesi. Gazi University Journal of Science Part C: Design and Technology, 11(3), Article 3. https://doi.org/10.29109/gujsc.1346056
14. Karmous, I., Pandey, A., Haj, K. B., & Chaoui, A. (2020). Efficiency of the Green Synthesized Nanoparticles as New Tools in Cancer Therapy: Insights on Plant-Based Bioengineered Nanoparticles, Biophysical Properties, and Anticancer Roles. Biological Trace Element Research, 196(1), 330–342. https://doi.org/10.1007/s12011-019-01895-0
15. Maciel, L. L. F., Silva, M. B., Moreira, R. O., Cardoso, A. P., Fernandes, C., Horn, A., de Aquino Almeida, J. C., & Kanashiro, M. M. (2022). In Vitro and In Vivo Relevant Antineoplastic Activity of Platinum(II) Complexes toward Triple-Negative MDA-MB-231 Breast Cancer Cell Line. Pharmaceutics, 14(10), Article 10. https://doi.org/10.3390/ pharmaceutics14102013
16. Mrid, R. B., Bouchmaa, N., Kabach, I., Zouaoui, Z., Chtibi, H., Maadoudi, M. E., Kounnoun, A., Cacciola, F., Majdoub, Y. O. E., Mondello, L., Zyad, A., & Nhiri, M. (2022). Dittrichia viscosa L. Leaves: A Valuable Source of Bioactive Compounds with Multiple Pharmacological Effects. Molecules, 27(7), Article 7. https://doi.org/10.3390/molecules27072108
17. Mssillou, I., Agour, A., Slighoua, M., Tourabi, M., Nouioura, G., Lyoussi, B., & Derwich, E. (2022). Phytochemical characterization, antioxidant activity, and in vitro investigation of antimicrobial potential of Dittrichia viscosa L. leaf extracts against nosocomial infections. Acta Ecologica Sinica, 42(6), 661–669. https://doi.org/10.1016/j.chnaes.2021.09.021
18. Ozkan, E., Pehlivan Karakas, F., Birinci Yildirim, A. B., Tas, I., Eker, I., Zeynep Yavuz, M., & Ucar Turker, A. (2019). Promising medicinal plant Inula viscosa L.: Antiproliferative, antioxidant, antibacterial and phenolic profiles. Progress in Nutrition, 21(3), 652–661. https://doi.org/10.23751/pn.v21i3.7186
19. Rhimi, W., Hlel, R., Ben Salem, I., Boulila, A., Rejeb, A., & Saidi, M. (2019). Dittrichia viscosa L. Ethanolic Extract Based Ointment with Antiradical, Antioxidant, and Healing Wound Activities. BioMed Research International, 2019, 4081253. https://doi.org/ 10.1155 /2019/4081253
20. Sevgi, E., Dag, A., Kızılarslan-Hançer, Ç., Atasoy, S., Kurt, B. Z., & Aksakal, Ö. (2021). Evaluation of cytotoxic and antioxidant potential of Dittrichia viscosa (L.) Greuter used in traditional medicine. Journal of Ethnopharmacology, 276, 114211. https://doi.org/10.1016/j.jep.2021.114211
21. Sevı̇ndı̇k, E., & Paksoy, M. Y. (2017). Aydın/Türkiye’de Yayılış Gösteren Dittrichia L. (Asteraceae) Cinsinin Kimyasal Kompozisyonunun Değerlendirilmesi. Türk Tarım ve Doğa Bilimleri Dergisi, 4(4), Article 4.
22. Sharma, D., Kumar, S., & Narasimhan, B. (2018). Estrogen alpha receptor antagonists for the treatment of breast cancer: A review. Chemistry Central Journal, 12(1), 107. https://doi.org/10.1186/s13065-018-0472-8
23. Sladonja, B., Poljuha, D., Krapac, M., Uzelac, M., & Mikulic-Petkovsek, M. (2021). Dittrichia viscosa: Native-Non Native Invader. Diversity, 13(8), Article 8. https://doi.org/10.3390/d13080380
24. Talib, W. H., & Mahasneh, A. M. (2010). Antiproliferative activity of plant extracts used against cancer in traditional medicine. Scientia Pharmaceutica, 78(1), 33–45. https://doi.org/10.3797/scipharm.0912-11
25. Togami, K., Yamaguchi, K., Chono, S., & Tada, H. (2017). Evaluation of permeability alteration and epithelial–mesenchymal transition induced by transforming growth factor-β1 in A549, NCI-H441, and Calu-3 cells: Development of an in vitro model of respiratory epithelial cells in idiopathic pulmonary fibrosis. Journal of Pharmacological and Toxicological Methods, 86, 19–27. https://doi.org/10.1016/j.vascn.2017.02.023
26. Top, R. (2018). Bazı önemli tıbbi bitkilerin antioksidan, antimikrobiyal ve antikanser etkilerinin araştırılması [masterThesis, Bartın Üniversitesi,Fen Bilimleri Enstitüsü]. https://acikerisim.bartin.edu.tr /handle/11772/495
27. Veiga, M., Costa, E. M., Silva, S., & Pintado, M. (2020). Impact of plant extracts upon human health: A review. Critical Reviews in Food Science and Nutrition, 60(5), 873–886. https://doi.org/10.1080/ 10408398. 2018.1540969
28. Yalçın, A. S., Yılmaz, A. M., Mutlu Altundağ, E., & Koçtürk, S. (2016). Kurkumin, kuersetin ve çay kateşinlerinin anti-kanser etkileri. Marmara Pharmaceutical Journal, 21(24530), 19–29. https://doi.org/ 10.12991/marupj.259877.