TÜRKİYE’DE YETİŞTİRİLEN 14 RUMEX TÜRÜNÜN İÇ PERİANT SEGMENTLERİNİN SİTOTOKSİSİTE TARAMA VE ANTİOKSİDAN KAPASİTE DEĞERLENDİRMESİ

Öz

Amaç: Meme kanseri dünya çapında en yaygın görülen kanser türlerinden biridir. Antioksidan kaynaklar kanserin oluşumunu önleyebilir. Dolayısıyla fenolikler açısından zengin doğal kaynaklar meme kanseri tedavisinde alternatif ajanlar sağlayabilir. Rumex türleri Türkiye florasında geniş bir dağılım göstermektedir. Bilimsel çalışmalar Rumex türlerinin çeşitli kanser hücreleri üzerindeki antitümöral özelliğine işaret etmektedir. Bu çalışmada, 14 Rumex türünün iç periant segmentlerinin etanolik ekstrelerinin farklı kökenlere sahip dört meme kanseri hücresi üzerinde test edilmeleri amaçlanmıştır. Ayrıca sağlıklı hücreler üzerindeki toksisiteleri de değerlendirilmiştir. Gereç ve Yöntem: Sitotoksisite ve toksisiteyi incelemek için resazurin redüksiyon yöntemi kullanılmıştır. Ayrıca; antioksidan profillerinin bir göstergesi olarak ekstrelerin fenolik içerikleri belirlenmiş ve DPPH, ABTS radikali süpürücü aktivite ve bakır iyonu redükleyici antioksidan kapasite yöntemleri ile antioksidan karakteristikleri belirlenmiştir. Sonuç ve Tartışma: Rumex türlerinin iç periant segmentlerinin etanolik ekstreleri, sağlıklı H9c2 sıçan miyoblastoma hücreleri üzerinde toksik olmamasına rağmen, meme kanseri hücreleri üzerinde dikkate değer sitotoksisite profilleri sergilememiştir. Ancak; genellikle yüksek fenolik içeriğe sahip güçlü antioksidan aktiviteler sergilemektedirler.

Anahtar Kelimeler

• Antioksidan
• meme kanseri
• rumex
• sitotoksisite
• total fenol

Proje Numarası

THD-2022-20462

CYTOTOXICITY SCREENING AND ANTIOXIDANT CAPACITY ASSESSMENT OF THE INNER PERIANTH SEGMENTS OF 14 RUMEX SPECIES GROWN IN TÜRKİYE

Öz

Objective: Breast cancer is one of the most prevalent cancer types worldwide. Antioxidant sources may prevent the occurrence of cancer. Natural sources rich in phenolics, thus, may provide alternate agents in the management of breast cancer. Rumex species are widely distributed in Turkish flora. Emerging evidence has pointed out the antitumoral property of Rumex species on a variety of cancer cells. In the present study, we propose to test the ethanolic extracts of the inner perianth segments of 14 Rumex species on four breast cancer cells with different origins. We also demonstrated their toxicity on healthy cells. Material and Method: We performed the resazurin reduction assay to examine the cytotoxicity and toxicity. Furthermore, we determined the phenolic contents of the extracts as an indicator of their antioxidant profile and ascertained their antioxidant activities by DPPH radical, ABTS radical cation scavenging activity and cupric ion-reducing antioxidant capacity assays. Result and Discussion: The ethanolic extracts of the inner perianth segments of Rumex species exhibited remarkable cytotoxicity profiles neither on breast cancer cells nor on healthy H9c2 rat myoblastoma cells. However, they usually displayed strong antioxidant activities due to possessing high phenolic content.

Anahtar Kelimeler

• Antioxidant
• breast cancer
• cytotoxicity
• rumex
• total phenol

Destekleyen Kurum

Hacettepe University Scientific Research Projects Unit

Proje Numarası

THD-2022-20462

Etik Beyan

The present study does not require The Ethics Committee Approval.

Teşekkür

A part of this study was supported by grants from Hacettepe University Scientific Research Projects Unit (Project No: THD-2022-20462).

Kaynakça

1. 1. Vasas, A., Orbán-Gyapai, O., Hohmann, J. (2015). The genus Rumex: Review of traditional uses, phytochemistry and pharmacology. Journal of Ethnopharmacology, 175, 198-228. [CrossRef]
2. 2. Li, J.J., Li, Y.X., Li, N., Zhu, H.T., Wang, D., Zhang, Y.J. (2022).The genus Rumex (Polygonaceae): An ethnobotanical, phytochemical and pharmacological review. Natural Products and Bioprospecting, 12(1), 21. [CrossRef]
3. 3. Munavu, R.M., Mudamba, L., Ogur, J. (1984). Isolation and characterization of the major anthraquinone pigments from Rumex abysinica. Planta Medica, 50(01), 111-111. [CrossRef]
4. 4. Lee, N.J., Choi, J.H., Koo, B.S., Ryu, S.Y., Han, Y.H., Lee, S.I., Lee, D.U. (2005). Antimutagenicity and cytotoxicity of the constituents from the aerial parts of Rumex acetosa. Biological and Pharmaceutical Bulletin, 28(11), 2158-2161. [CrossRef]
5. 5. Dénes, A., Papp, N., Babai, D., Czúcz, B., Molnár, Z. (2013). Edible wild plants and their use based on ethnographic and ethnobotanical researches among Hungarian in the Carpathian Basin. Dunántúli Dolgozatok (A) Természettudományi Sorozat. 13, 35-76.
6. 6. Cakilcioglu, U., Turkoglu, I. (2010). An ethnobotanical survey of medicinal plants in Sivrice (Elazığ-Turkey). Journal of Ethnopharmacology, 132(1), 165-175. [CrossRef]
7. 7. Turkish Plants Data Service Web site (2023). Retrieved August 22, 2023, from http://194.27.225.161/yasin/tubives/index.php?sayfa=hizli_ara. Accessed date: 22.08.2023.
8. 8. Davis, P.H. (1970). Flora of Turkey and the East Aegean Islands. University Press, Edinburgh.

9. 9. Davis, P., Miller, R., Tan, K. (1988). Flora of Turkey. University Press, Edinburgh.
10. 10. Süleyman, H., Demirezer, L.Ö., Kuruüzüm, A., Banoğlu, Z.N., Göçer, F., Özbakir, G., Gepdiremen, A. (1999). Antiinflammatory effect of the aqueous extract from Rumex patientia L. roots. Journal of Ethnopharmacology, 65(2), 141-148. [CrossRef]
11. 11. Demirezer, L.O., Kuruüzüm-Uz, A., Bergere, I., Schiewe, H.J., Zeeck, A. (2001). The structures of antioxidant and cytotoxic agents from natural source: Anthraquinones and tannins from roots of Rumex patientia. Phytochemistry, 58(8), 1213-1217. [CrossRef]
12. 12. Demirezer, O., Kuruüzüm, A., Bergere, I., Schiewe, H.J., Zeeck, A. (2001). Five naphthalene glycosides from the roots of Rumex patientia. Phytochemistry, 56(4), 399-402.
13. 13. Özenver, N., Saeed, M., Demirezer, L.O., Efferth, T. (2018). Aloe-emodin as drug candidate for cancer therapy. Oncotarget, 9(25), 17770-17796. [CrossRef]
14. 14. Süleyman, H., Demirezer, L.O., Kuruüzüm-Uz, A., Akçay, F. (2002). Gastroprotective and antiulcerogenic effects of Rumex patientia L. extract. Pharmazie, 57(3), 204-205.
15. 15. Kuruüzüm, A., Demirezer, L.O., Bergere, I., Zeeck, A. (2001). Two new chlorinated naphthalene glycosides from Rumex patientia. Journal of Natural Products, 64(5), 688-690. [CrossRef]
16. 16. Demirezer, L.O., Kuruüzüm-Uz, A. (2014). Rapid and simple biological activity of some Rumex species; evaluation of bioguided fractions of R. scutatus and pure compounds. Zeitschrift fur Naturforschung C, 52, 461-462. [CrossRef]
17. 17. Uzun, M., Demirezer, L.O. (2019). Anti-aging power of Rumex crispus L.: Matrixmetalloproteinases inhibitor, sun protective and antioxidant. South African Journal of Botany, 124, 364-371. [CrossRef]
18. 18. Uzun, M., Guvenalp, Z., Kazaz, C., Demirezer, L.O. (2020). Matrix metalloproteinase inhibitor and sunscreen effective compounds from Rumex crispus L.: Isolation, identification, bioactivity and molecular docking study. Phytochemisty Analysis, 31(6), 818-834. [CrossRef]
19. 19. Özenver, N., Güvenalp, Z., Kuruüzüm-Uz, A., Demirezer, L.O. (2020). Inhibitory potential on key enzymes relevant to type II diabetes mellitus and antioxidant properties of the various extracts and phytochemical constituents from Rumex acetosella L. Journal of Food Biochemistry, 44(10), e13415. [CrossRef]
20. 20. Demirezer, L.O. (1994). Anthraquinones from Rumex gracilescens Rech. and Rumex crispus L. Pharmazie, 49(5), 378-379. [CrossRef]
21. 21. Demirezer, L.O. (1994). Concentrations of anthraquinone glycosides of Rumex crispus during different vegetation stages. Zeitschrift für Naturforschung, 49, 404-406. [CrossRef]
22. 22. World Health Organization Website. (2023). Retrieved August 22, 2023, from https://www.who.int/news-room/fact-sheets/detail/breast-cancer. Accessed date: 22.08.2023.
23. 23. Newman, D.J., Cragg, G.M. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products, 83(3), 770-803. [CrossRef]
24. 24. Hayes, J.D., Dinkova-Kostova, A.T., Tew, K.D. (2020). Oxidative stress in cancer. Cancer Cell, 38(2), 167-197. [CrossRef]
25. 25. Sosa, V., Moliné, T., Somoza, R., Paciucci, R., Kondoh, H., LLeonart, M.E. (2013). Oxidative stress and cancer: An overview. Ageing Research Reviews, 12(1), 376-390. [CrossRef]
26. 26. Visconti, R., Grieco, D. (2009). New insights on oxidative stress in cancer. Current Opinion in Drug Discovery and Development, 12(2), 240-245.
27. 27. Maestri, D., Nepote, V., Lamarque, A., Zygadlo, J. (2006). Natural products as antioxidants. Phytochemistry, 37(661), 105-135.
28. 28. Leonard, S.S., Keil, D., Mehlman, T., Proper, S., Shi, X., Harris, G.K. (2006). Essiac tea: Scavenging of reactive oxygen species and effects on DNA damage. Journal of Ethnopharmacology, 103(2), 288-296. [CrossRef]
29. 29. ATTC Web site. (2023). Retrieved August 28, 2023, from https://www.atcc.org. Accessed date: 28.08.2023.
30. 30. O’Brien, J., Wilson, I., Orton, T., Pognan, F. (2000). Investigation of the alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. European Journal of Biochemistry. 267, 5421-5426. [CrossRef]
31. 31. Kuete, V., Mbaveng, A.T., Nono, E.C., Simo, C.C., Zeino, M., Nkengfack, A.E., Efferth, T. (2016). Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells. Phytomedicine, 23, 856-863. [CrossRef]
32. 32. Arıtuluk, Z., Çankaya, I.I., Özkan, A.M.G. (2016). Antioxidant activity, total phenolic and flavonoid contents of some Tanacetum L. (Asteraceae) taxa growing in Turkey. Fabad Journal of Pharmaceutical Sciences, 41, 17-25.
33. 33. Jensen, S.R., Gotfredsen, C.H., Harput, U.S., Saracoglu, I. (2010). Chlorinated iridoid glucosides from Veronica longifolia and their antioxidant activity. Journal of Natural Products, 73(9), 1593-1596. [CrossRef]
34. 34. Erel, O. (2004). A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clinical Biochemistry, 37(4), 277-285. [CrossRef]
35. 35. Chatterjee, K., Zhang, J., Honbo, N., Karliner, J.S. (2010). Doxorubicin cardiomyopathy. Cardiology, 115(2), 155-162. [CrossRef]
36. 36. Volkova, M., Russell, R. (2011). Anthracycline cardiotoxicity: Prevalence, pathogenesis and treatment. Current Cardiology Reviews, 7(4), 214-220. [CrossRef]
37. 37. Rawat, P.S., Jaiswal, A., Khurana, A., Bhatti, J.S., Navik, U. (2021). Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomedicine & Pharmacotherapy, 139, 111708. [CrossRef]
38. 38. Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., Bitto, A. (2017). Oxidative stress: Harms and benefits for human health. Oxidative Medicine and Cellular Longevity, 2017, 8416763. [CrossRef]
39. 39. Dasgupta, A., Klein, K. (2014) Methods for measuring oxidative stress in the laboratory. In: A. Dasgupta and K. Klein (Eds). Antioxidants in Food, Vitamins and Supplements, (pp. 19-40). USA: Elsevier.
40. 40. Sujarwo, W., Keim, A.P. (2019). Spondias pinnata (L. f.) Kurz. (Anacardiaceae): Profiles and applications to diabetes. In: R.R. Watson and V.R. Preedy (Eds.), Bioactive food as dietary interventions for diabetes (Second Edition), (pp. 395-405). United Kingdom: Academic Press.
41. 41. Shahidi, F., Zhong, Y. (2015). Measurement of antioxidant activity. Journal of Functional Foods. 18, 757-781. [CrossRef]
42. 42. Apak, R., Güçlü, K., Ozyürek, M., Karademir, S.E. (2004). Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method. Journal of Agricultural Food Chemistry, 52(26), 7970-7981. [CrossRef]
43. 43. Boik, J. (2001). Natural Compounds in Cancer Therapy, Oregon Medical Press, Princeton.
44. 44. Mbaveng, A.T., Damen, F., Simo Mpetga, J.D., Awouafack, M.D., Tane, P., Kuete, V., Efferth, T. (2019). Cytotoxicity of crude extract and isolated constituents of the Dichrostachys cinerea Bark towards multifactorial drug-resistant cancer cells. Evidence Based Complementary and Alternative Medicine, 2019, 8450158. [CrossRef]
45. 45. Suffness, M., Pezzuto, J.M., Hostettmann, K. (1990). Methods in plant biochemistry: Assays for bioactivity. In: K. Hostettmann (Ed.), Methods in Plant Biochemistry, (pp: 33-71). London: Academic Press.
46. 46. Al Jitan, S., Alkhoori, S.A., Yousef, L.F. (2018). Phenolic acids from plants: Extraction and application to human health. In: R. Atta Ur (Ed.), Studies in Natural Products Chemistry, (pp.389-417). United Kingdom: Elsevier.
47. 47. de la Rosa, L.A., Moreno-Escamilla, J.O., Rodrigo-García, J., Alvarez-Parrilla, E. (2019). Phenolic compounds. In: E.M. Yahia and A. Carrillo-Lopez (Eds.), Postharvest Physiology and Biochemistry of Fruits and Vegetables, (pp. 253-271). United Kingdom: Woodhead Publishing.
48. 48. do Carmo, M.A.V., Granato, D., Azevedo, L. (2021). Antioxidant/pro-oxidant and antiproliferative activities of phenolic-rich foods and extracts: A cell-based point of view. In: D. Granato, (Ed.), Advances in Food Nutrition Research, (pp.253-280). India: Academic Press.
49. 49. Ahmad, S., Ullah, F., Zeb, A., Ayaz, M., Ullah, F., Sadiq, A. (2016). Evaluation of Rumex hastatus D. Don for cytotoxic potential against HeLa and NIH/3T3 cell lines: Chemical characterization of chloroform fraction and identification of bioactive compounds. BMC Complementary and Alternative Medicine, 16(1), 308. [CrossRef]
50. 50. Saoudi, M.M., Bouajila, J., Rahmani, R., Alouani, K. (2021). Phytochemical composition, antioxidant, antiacetylcholinesterase, and cytotoxic activities of Rumex crispus L. International Journal of Analytical Chemistry, 2021, 6675436. [CrossRef]
51. 51. Boyali, F. (2023). PhD Thesis. Türkiye’de yetişen Rumex türleri üzerinde HPLC ile kemotaksonomik araştırmalar ve temel bileşen analizi. Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.