Dereotu (Anethum graveolens) İnsan Yumurtalık Kanseri Hücre Hattı A2780 Üzerinde DNA Hasarına Neden Olmadan Hücre Ölümünü İndükler

Abstract

Entobotanik çalışmalar dereotunun (Anethum graveolens) antibakteriyal ve antioksidan etki sergilediğini ve bazı kanser türleri üzerine baskılayıcı özellik gösterdiği bildirilmektedir. Bu çalışmada dereotunun, insan yumurtalık kanseri hücre serisine karşı sitotoksik ve genotoksik etkilerini belirlemeyi amaçladık. Dereotu özütünün farklı konsantrasyonları insan yumurtalık kanseri hücre hattı (A2780) üzerine uygulandıktan sonra, özütün hücre canlılığı üzerine etkileri 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür (MTT) testi ile belirlendi. Sonrasında, sitotoksik etki gösteren dozların hüre DNA’sı üzerine genotoksik etkileri tek hücre jel elektroforezi (Comet) yöntemi ile ortaya konuldu. Dereotunun 600 µg/mL ve üzeri dozları hücre canlılığını kontrol grubuna kıyasla önemli düzeyde azalttı (p<0.05). Sitotoksik etki artan dozlarda daha belirgindi. Comet analizleri sonucunda A2780 hücrelerinde uygulamalar sonrası DNA hasarında anlamlı bir değişikliğin meydana gelmediği belirlendi. Elde edilen bu sonuçlar dereotunun DNA hasarına neden olmadan hücre canlılığını farklı mekanizmalar üzerinden azalttığını düşündürmektedir.

Keywords

• Dereotu
• Anethum graveolens
• Yumurtalık kanseri
• Sitotoksisite
• Genotoksisite

Dill (Anethum graveolens) Induces Cell Death in a Human Ovarian Cancer Cell Line, A2780, without Causing DNA Damage

Abstract

Ethnobotanical studies have reported that dill (Anethum graveolens) exhibits antibacterial and antioxidant effects and shows suppressive properties on some cancer types. In this study, we aimed to determine the cytotoxic and genotoxic effects of dill against human ovarian cancer cell lines. After different concentrations of dill extract were applied on human ovarian cancer cell line (A2780), the effects of the extract on cell viability were determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, the genotoxic effects of cytotoxic doses on wild-type DNA were determined by single-cell gel electrophoresis (Comet). Dill doses of 600 µg/mL and above significantly decreased cell viability compared to the control group (p<0.05). The cytotoxic effect was more pronounced at increasing doses. As a result of Comet analysis, it was determined that no significant change in DNA damage occurred in A2780 cells after the treatments. These results suggest that dill reduces cell viability through different mechanisms without causing DNA damage.

Keywords

• Dill
• Anethum graveolens
• Ovarian cancer
• Cytotoxicity
• Genotoxicity

References

1. Al-Oqail, M. M. ve Farshori, N. N. (2021). Antioxidant and Anticancer Efficacies of Anethum graveolens against Human Breast Carcinoma Cells through Oxidative Stress and Caspase Dependency. Biomed Res Int, 2021: 5535570.
2. Al-Sheddi, E. S., Al-Zaid, N. A., Al-Oqail, M. M., Al-Massarani, S. M., El-Gamal, A. A. ve Farshori, N. N. (2019). Evaluation of cytotoxicity, cell cycle arrest and apoptosis induced by Anethum graveolens L. essential oil in human hepatocellular carcinoma cell line. Saudi Pharm J, 27(7): 1053-1060.
3. Cavalheri, V. ve Granger, C. L. (2020). Exercise training as part of lung cancer therapy. Respirology, 25 Suppl 2: 80-87.
4. Cortez, A. J., Tudrej, P., Kujawa, K. A. ve Lisowska, K. M. (2018). Advances in ovarian cancer therapy. Cancer Chemother Pharmacol, 81(1): 17-38.
5. Delaquis, P. J., Stanich, K., Girard, B. ve Mazza, G. (2002). Antimicrobial activity of individual and mixed fractions of dill, cilantro, coriander and eucalyptus essential oils. Int J Food Microbiol, 74(1-2): 101-109.
6. Deli, T., Orosz, M. ve Jakab, A. (2020). Hormone Replacement Therapy in Cancer Survivors - Review of the Literature. Pathol Oncol Res, 26(1): 63-78.
7. Erden, Y. (2020). Capsanthin Stimulates the Mitochondrial Apoptosis-Mediated Cell Death, following DNA Damage in MCF-7 Cells. Nutrition and Cancer: 1-9.
8. Erden, Y. (2021). Sour black mulberry (Morus nigra L.) causes cell death by decreasing mutant p53 expression in HT-29 human colon cancer cells. Food Bioscience, 42: 101113.

9. Goodarzi, M. T., Khodadadi, I., Tavilani, H. ve Abbasi Oshaghi, E. (2016). The Role of Anethum graveolens L. (Dill) in the Management of Diabetes. J Trop Med, 2016: 1098916.
10. Jana, S. ve Shekhawat, G. S. (2010). Anethum graveolens: An Indian traditional medicinal herb and spice. Pharmacogn Rev, 4(8): 179-184.
11. Luo, J., Solimini, N. L. ve Elledge, S. J. (2009). Principles of cancer therapy: oncogene and non-oncogene addiction. Cell, 136(5): 823-837.
12. Mohammed, F. A., Elkady, A. I., Syed, F. Q., Mirza, M. B., Hakeem, K. R. ve Alkarim, S. (2018). Anethum graveolens (dill) - A medicinal herb induces apoptosis and cell cycle arrest in HepG2 cell line. J Ethnopharmacol, 219: 15-22.
13. 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.
14. NIH. "Cancer Stat Facts: Ovarian Cancer". from https://seer.cancer.gov/statfacts/html/ovary.html. Son erişim tarihi:28/12/2022).
15. Patra, S., Pradhan, B., Nayak, R., Behera, C., Das, S., Patra, S. K., Efferth, T., Jena, M. ve Bhutia, S. K. (2021). Dietary polyphenols in chemoprevention and synergistic effect in cancer: Clinical evidences and molecular mechanisms of action. Phytomedicine, 90: 153554.
16. Satyanarayana, S., Sushruta, K., Sarma, G. S., Srinivas, N. ve Subba Raju, G. V. (2004). Antioxidant activity of the aqueous extracts of spicy food additives--evaluation and comparison with ascorbic acid in in-vitro systems. J Herb Pharmacother, 4(2): 1-10.
17. Singh, N. P., McCoy, M. T., Tice, R. R. ve Schneider, E. L. (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res, 175(1): 184-191.
18. Tavakkol Afshari, H. S., Homayouni Tabrizi, M., Ardalan, T., Jalili Anoushirvani, N. ve Mahdizadeh, R. (2022). Anethum Graveolens Essential Oil Nanoemulsions (AGEO-NE) as an Exclusive Apoptotic Inducer in Human Lung Adenocarcinoma (A549) Cells. Nutr Cancer, 74(4): 1411-1419.
19. Wang, Y., Yu, H., Zhang, J., Gao, J., Ge, X. ve Lou, G. (2015). Hesperidin inhibits HeLa cell proliferation through apoptosis mediated by endoplasmic reticulum stress pathways and cell cycle arrest. BMC Cancer, 15(1): 682.
20. Wild, C., Weiderpass, E. ve Stewart, B. (2020). World cancer report: cancer research for cancer prevention. Lyon: International Agency for Research on Cancer.
21. Wilson, D. J. (2017). Exercise for the Patient after Breast Cancer Surgery. Semin Oncol Nurs, 33(1): 98-105.
22. Yazdanparast, R. ve Alavi, M. (2001). Antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves after the removal of furocoumarins. Cytobios, 105(410): 185-191.
23. Zhou, Y., Zheng, J., Li, Y., Xu, D. P., Li, S., Chen, Y. M. ve Li, H. B. (2016). Natural Polyphenols for Prevention and Treatment of Cancer. Nutrients, 8(8).