Celtis australis Exhibits Cytotoxic Effects by Inducing DNA Damage in Human Ovarian Cancer Cells

Year 2024, Volume: 13 Issue: 1, 7 - 11, 26.03.2024

Gülsüm Nur Fidan Sevilay Günay Yavuz Erden

https://doi.org/10.46810/tdfd.1348574

Abstract

Native to the Mediterranean and southwest Asia, Celtis australis is used in folk medicine to treatment of many diseases such as peptic ulcer, diarrhea, dysentery, pain, and colic. However, there are very few studies on the effects of this species on cancer. We report for the first time the cytotoxic and genotoxic properties of C. australis on the human ovarian cancer cell line A2780.
In the study, C. australis extract prepared in ethanol/phosphate buffer was applied to A2780 cells. The change in viability level in A2780 cells after treatment was determined by MTT assay and DNA damage was determined by single-cell gel electrophoresis (Comet) analysis.
Our results showed that plant extract application at doses above 200 µg/ml significantly decreased A2780 cell viability (p<0.05). The IC50 value for A2780 cells of C. australis was determined as 251.43 μg/ml. Comet analysis results revealed that 50 µg/ml and above dose applications increased the level of DNA damage (p<0.05). These results suggest that C. australis mediates cell death by inducing DNA damage in A2780 cancer cells.

Keywords

Ovarian cancer, Celtis Australis, Cytotoxicity, DNA Damage

Project Number

1919B012111685

References

• Jiramongkol Y, Lam EW. FOXO transcription factor family in cancer and metastasis. Cancer Metastasis Rev. 2020;39(3):681-709.
• Wild C, Weiderpass E, Srewart B. World cancer report. International agency for research on cancer: WHO; 2020.
• Kara F, Keskinkılıç B. Türkiye kanser istatistikleri 2017 Ankara: T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü; 2021 [updated 17.11.2021. Available from: https://hsgm.saglik.gov.tr/depo/birimler/kanser-db/istatistik/Turkiye_Kanser_Istatistikleri_2017.pdf.
• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
• Romero-Sandoval EA, Fincham JE, Kolano AL, Sharpe BN, Alvarado-Vazquez PA. Cannabis for chronic pain: Challenges and considerations. Pharmacotherapy. 2018;38(6):651-62.
• Shaito A, Thuan DTB, Phu HT, Nguyen THD, Hasan H, Halabi S, Abdelhady S, Nasrallah GK, Eid AH, Pintus G. Herbal medicine for cardiovascular diseases: Efficacy, mechanisms, and safety. Front Pharmacol. 2020;11:422.
• Ota A, Visnjevec AM, Vidrih R, Prgomet Z, Necemer M, Hribar J, Cimerman NG, Mozina SS, Bucar-Miklavcic M, Ulrih NP. Nutritional, antioxidative, and antimicrobial analysis of the Mediterranean hackberry (Celtis australis L.). Food Sci Nutr. 2017;5(1):160-70.
• Spitaler R, Gurschler S, Ellmerer E, Schubert B, Sgarbossa M, Zidorn C. Flavonoids from Celtis australis (Cannabaceae). Biochem Syst Ecol. 2009;37(2):120-1.
• Zehrmann N, Zidorn C, Ganzera M. Analysis of rare flavonoid C-glycosides in Celtis australis L. by micellar electrokinetic chromatography. J Pharm Biomed Anal. 2010;51(5):1165-8.
• El-Alfy TS, El-Gohary HM, Sokkar NM, Hosny M, Al-Mahdy DA. A new flavonoid C-glycoside from Celtis australis L. and Celtis occidentalis L. leaves and potential antioxidant and cytotoxic activities. Sci Pharm. 2011;79(4):963-75.
• Acquaviva R, Sorrenti V, Santangelo R, Cardile V, Tomasello B, Malfa G, Vanella L, Amodeo A, Genovese C, Mastrojeni S, Pugliese M, Ragusa M, Di Giacomo C. Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures. Oncol Rep. 2016;36(4):2298-304.
• Krief S, Hladik CM, Haxaire C. Ethnomedicinal and bioactive properties of plants ingested by wild chimpanzees in Uganda. J Ethnopharmacol. 2005;101(1-3):1-15.
• Koduru S, Grierson DS, Afolayan AJ. Ethnobotanical information of medicinal plants used for treatment of cancer in the Eastern Cape Province, South Africa. Curr Sci. 2007;92(7):906-8.
• Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
• Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184-91.
• Bioquest A. "Quest Graph™ IC50 Calculator." AAT Bioquest, Inc. 2021 [updated 14.04.2021. Available from: https://www.aatbio.com/tools/ic50-calculator.
• Shen CY, Jiang JG, Yang L, Wang DW, Zhu W. Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. Br J Pharmacol. 2017;174(11):1395-425.
• Dhanjal DS, Bhardwaj S, Sharma R, Bhardwaj K, Kumar D, Chopra C, Nepovimova E, Singh R, Kuca K. Plant fortification of the diet for anti-ageing effects: A review. Nutrients. 2020;12(10):3008.
• Shin SA, Moon SY, Kim WY, Paek SM, Park HH, Lee CS. Structure-based classification and anti-cancer effects of plant metabolites. Int J Mol Sci. 2018;19(9):2651.
• Safari F, Hassanpour H, Alijanpour A. Evaluation of hackberry (Celtis australis L.) fruits as sources of bioactive compounds. Sci Rep. 2023;13(1):12233.
• Badoni R, Semwal DK, Rawat U, Rawat M. Chemical constituents from fruits and stem bark of Celtis australis L. Helvetica Chimica Acta. 2011;94:464-73.
• Acquaviva R, Sorrenti V, Santangelo R, Cardile V, Tomasello B, Malfa G, Vanella L, Amodeo A, Genovese C, Mastrojeni S. Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures. Oncol Rep. 2016;36(4):2298-304.
• Hwang BY, Chai H-B, Kardono LBS, Riswan S, Farnsworth NR, Cordell GA, Pezzuto JM, Douglas Kinghorn A. Cytotoxic triterpenes from the twigs of Celtis philippinensis. Phytochemistry. 2003;62(2):197-201.