ARCTİUM MİNUS METANOL EKSTRESİNİN ÇEŞİTLİ KANSER HÜCRE HATLARI ÜZERİNDE SİTOTOKSİK ETKİLERİ

Year 2022, , 742 - 754, 30.09.2022

Ayşe Arzu Şakul , Yasemin Yozgat Byrne , Ayşe Esra Karadağ , Ebrar Altınalan , Şeyma Çimen , Mehmet Evren Okur

https://doi.org/10.33483/jfpau.1084639

Abstract

Amaç: Bu çalışmada Arctium minus (Hill) Bernh. ssp. minus’un toprak üstü kısımlarından elde edilen metanol ekstresinin kanser hücre hatları üzerindeki sitotoksik etkilerinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Arctium minus (Hill) Bernh. ssp. minus’un metanol ekstresinin, iki farklı insan meme kanseri hücre hattına (MCF-7 ve MDA-MB-231) ve kontrol olarak normal insan fibroblast hücre hattına (MRC-5) uygulanması ile in vitro sitotoksik etkileri araştırılmıştır. Hücre canlılık tayini CellTiter-Blue metodu kullanılarak gerçekleştirilmiştir. İstatistiksel analiz için One-Way ANOVA ve Tukey post-hoc testi kullanılmıştır.
Sonuç ve Tartışma: Analizlerde, MCF-7 kanser hücrelerinde hücre canlılığı %27,8 -38,7 oranında belirlenmiş olup önemli derecede sitotoksik aktivite tespit edilmiştir (1 mg/mL ekstre uygulaması için p<0.022). Ancak MDA-MB-231 kanser hücre hatlarında %47,8-59,7 oranında hücre canlılığı gözlemlenmiştir. MRC-5 normal fibroblast hücrelerinde ise sitotoksisite gözlemlenmemiştir (%92,4 – 105,4 hücre canlılığı). Bu bulgulardan yola çıkarak, MCF-7 kanser hücreleri ve MRC5 normal fibroblast hücrelerine 1,25 mg/mL Arcitum minus ekstresi ile muamele edilmiş ve flow sitometrisi metodu ile hücre ölümünün ölçümü gerçekleştirilmiştir. Arctium minus ekstresi uygulaması ile hücre ölümü, MCF-7 kanser hücrelerinde (%98) MRC5 normal fibroblast hücrelerinden (%25) çok daha yüksek oranda gerçekleşmiştir. Sonuç olarak, Arctium minus ssp. minus ekstresi uygulamasının hücre canlılığını MCF-7 hücre hattında normal fibroblast hücre hattına göre daha fazla azalttığı söylenilebilir.

Keywords

Arctium minus ssp. minus, hücre canlılığı, hücre ölümü, kanser, sitotoksisite

Supporting Institution

İstanbul Medipol Üniversitesi

CYTOTOXIC EFFECTS OF ARCTIUM MINUS METHANOL EXTRACT ON VARIOUS CANCER CELL LINES

Abstract

Objective: This study aimed to evaluate the cytotoxic effects of Arctium minus (Hill) Bernh. ssp. minus methanol extract derived from aerial parts on cancer cell lines.
Material and Method: For cytotoxicity assays, two different human breast cancer cell lines (MCF-7 and MDA-MB-231) and healthy human fibroblast cell line (MRC-5)as a control were used. Cell viability determination was performed using the CellTiter-Blue method. One-Way ANOVA and Tukey post test were used for statistical analysis.
Result and Discussion: Cell viability has been detected between ratios of 27.8-38.7% for MCF-7 cancer cell line, and a significant cytotoxic activity was observed via the analysis (1 mg/mL extract treatment p< 0.022). However, 47.8-59.7% cell viability was observed for MDA-MB-231 cancer cell line, and MRC-5 healthy fibroblast cell line did not demonstrate any cell viability (92.4-105.4% cell viability). Depending on these data, MCF-7 cancer cell line and MRC-5 fibroblast healthy cell line were treated with Arcitum minus extract, then cell viability was detected by flow cytometry technique. The ratio of the cell death was higher in MCF-7 cancer cell line (98%) compared with the MRC-5 fibroblast healthy cell line (25%) after the Arctium minus extract treatment. In conclusion, Arctium minus ssp. minus extract has significantly decreased the cell viability in MCF-7 cancer cell line when compared with the MCR-5 fibroblast normal cell line. 

Keywords

Arctium minus ssp. minus, cancer, cell death, cell viability, cytotoxicity

References

• 1. Futreal, P. A., Kasprzyk, A., Birney, E., Mullikin, J. C., Wooster, R., Stratton, M. R. (2001). Cancer and genomics. Nature, 409(6822), 850-852. [CrossRef]
• 2. Global Cancer Observatory Web Site. (2020) From: https://gco.iarc.fr/today/home Erişim Tarihi: 28.04.2022
• 3. Banik, K., Harsha, C., Bordoloi, D., Lalduhsaki Sailo, B., Sethi, G., Leong, H. C., Arfuso, F., Mishra, S., Wang, L., Kumar, A. P., Kunnumakkara, A. B. (2018). Therapeutic potential of gambogic acid, a caged xanthone, to target cancer. Cancer Letters, 416, 75-86. [CrossRef]
• 4. Top, R., Erden, Y., Tekin, S. (2019). Bazı önemli tıbbi bitkilerin antioksidan ve antikanser etkilerinin araştırılması. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 8(2), 435-442. [CrossRef]
• 5. Wang, D., Bădărau, A. S., Swamy, M. K., Shaw, S., Maggi, F., da Silva, L. E., López, V., Yeung, A. W. K., Mocan, A., Atanasov, A. G. (2019). Arctium Species Secondary Metabolites Chemodiversity and Bioactivities. Frontiers in Plant Science, 10, 834. [CrossRef]
• 6. Avrupa Fitoterapi Bilimsel Kooperatifi-Bitkisel Tıbbi Ürünler Bilimsel Vakfı (2016). Arctii radix (Burdock Root) üzerine ESCOP Monografisi. From: http://escop.com/downloads/arctii/ Erişim Tarihi: 28.04.2022
• 7. Kupicha FK. (1975). Arctium minus (Hill) Bernh. Içinde Flora of Turkey and the East Aegean Islands.
• 8. Washino, T., Yoshikura, M., Obata, S. (1986). New Sulfur-containing Acetylenic Compounds from Arctium lappa. Agricultural and Biological Chemistry, 50(2), 263–269. [CrossRef]
• 9. Xiao, W., Chuange, C., Yutao, Y., Chengchao, Z. (2004). Analysis of the essential oil from Arctium lappa L. Natural Product Research and Development, 16(1), 33–35.
• 10. Washing, T., Kobayashi, H., Ikawa, Y. (1987). Structures of Lappaphen-a and Lappaphen-b, new guaianolides linked with a sulfur-containing acetylenic compound, from Arctium lappa L. Agricultural and Biological Chemistry, 51(6), 1475-1480.
• 11. Lin, S., Chung, T., Lin, C., Ueng, T.-H., Lin, Y., Lin, S., Wang, L. (2000). Hepatoprotective Effects of Arctium Lappa on Carbon Tetrachloride- and Acetaminophen-Induced Liver Damage. The American Journal of Chinese Medicine, 28(02), 163-173. [CrossRef]
• 12. Ahangarpour, A., Heidari, H., Oroojan, A. A., Mirzavandi, F., Nasr Esfehani, K., Dehghan Mohammadi, Z. (2017). Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice. Avicenna Journal of Phytomedicine, 7(2), 169-179. [CrossRef]
• 13. Altundağ, E., Ozturk, M. (2011). Ethnomedicinal studies on the plant resources of east Anatolia, Turkey. Procedia - Social and Behavioral Sciences, 19, 756-777 [CrossRef]
• 14. Tuzlacı, E., Erol, M. K. (1999). Turkish folk medicinal plants. Part II: Eğirdir (Isparta). Fitoterapia, 6, 593-610. [CrossRef]
• 15. Güner, A., Aslan, S., Ekim, T., Vural, M., Babaç, M. T. (2012). Türkiye Bitkileri Listesi (Damarlı Bitkiler. Nezahat Gökyiğit Botanik Bahçesi ve Flora Araştırmaları Derneği.
• 16. Lubian, C. T., Teixeira, J. M., Lund, R. G., Nascente, P. S., Del Pino, F. (2010). Antifungal activity of the aqueous extract from Arctium minus (Hill) Bernh. (Asteraceae) on oral Candida species. Brazilian Journal of Medicinal Plants, 12(2), 157-162. [CrossRef]
• 17. Altay, V., Karahan, F. (2017). Medicinal Plants Used to Sunstroke and Sunburn Treatment in Anatolian Traditional Medicine. Erzincan University Journal of Science and Technology, 2017, 124–137. [CrossRef]
• 18. Fujita, T., Sezik, E., Tabata, M., Yesilada, E., Honda, G., Takeda, Y., Tanaka, T., Takaishi, Y. (1995). Traditional medicine in Turkey VII. Folk medicine in middle and west Black Sea regions. Economic Botany, 49(4), 406. [CrossRef]
• 19. European Medicines Agency web site (2011). From: https://www.ema.europa.eu/documents /herbal-monograph/final-community-herbal-monograph-arctium-lappa-l-radix_en.pdf Erişim Tarihi 03.03.2021
• 20. Erdemoglu, N., Turan, N. N., Akkol, E. K., Sener, B., Abacioglu, N. (2009). Estimation of anti-inflammatory, antinociceptive and antioxidant activities of Arctium minus (Hill) Bernh. ssp. minus. Journal of Ethnopharmacology, 121(2), 318-323. [CrossRef]
• 21. Fischer, S. P. M., Brusco, I., Camponogara, C., Piana, M., Faccin, H., Gobo, L. A., de Carvalho, L. M., Oliveira, S. M. (2018). Arctium minus crude extract presents antinociceptive effect in a mice acute gout attack model. Inflammopharmacology, 26(2), 505-519. [CrossRef]
• 22. Boldizsár, I., Füzfai, Z., Tóth, F., Sedlák, E., Borsodi, L., Molnár-Perl, I. (2010). Mass fragmentation study of the trimethylsilyl derivatives of arctiin, matairesinoside, arctigenin, phylligenin, matairesinol, pinoresinol and methylarctigenin: their gas and liquid chromatographic analysis in plant extracts. Journal of Chromatography. A, 1217(10), 1674-1682. [CrossRef]
• 23. Predes, F. S., Ruiz, A. L. T. G., Carvalho, J. E., Foglio, M. A., Dolder, H. (2011). Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. BMC Complementary and Alternative Medicine, 11(1), 25. [CrossRef]
• 24. Zhou, X., Zhang, H., Ge, L., Gong, H., Tian, S. (2011). Determination of Arctiin and Arctigenin Contents in Arctium Tomentosum Mill. by HPLC Method. Journal of Chemistry, 8, S372-S376. [CrossRef]
• 25. Eroğlu Köksal, E. (2019). Yüksek Lisans Tezi. Meme Kanserinde Doğal Biyoaktif Bileşenlerin Antikanser Etkilerinin Karşilaştirmali Araştırılması. Yıldırım Beyazıt Üniversitesi, Ankara, Türkiye.
• 26. Riccardi, C., Nicoletti, I. (2006). Analysis of apoptosis by propidium iodide staining and flow cytometry. Nature Protocols 1, 1458–1461. [CrossRef]
• 27. Ge, L., Liu, F., Hu, Y., Zhou, X. (2020). Qualitative and quantitative analysis of arctiin and arctigenin in Arctium tomentosum Mill. by high-performance thin-layer chromatography. JPC - Journal of Planar Chromatography - Modern TLC, 33, 1–8. [CrossRef]
• 28. Liu, S., Chen, K., Schliemann, W., Strack, D. (2005). Isolation and identification of arctiin and arctigenin in leaves of burdock (Arctium lappa L.) by polyamide column chromatography in combination with HPLC-ESI/MS. Phytochemical Analysis : PCA, 16(2), 86–89. [CrossRef]
• 29. Lee, C.-Y., Hsin, M.-C., Chen, P.-N., Lin, C.-W., Wang, P.-H., Yang, S.-F., Hsiao, Y.-H. (2022). Arctiin Inhibits Cervical Cancer Cell Migration and Invasion through Suppression of S100A4 Expression via PI3K/Akt Pathway. Pharmaceutics, 14(2), 365. [CrossRef]
• 30. Gest, C., Joimel, U., Huang, L., Pritchard, L.-L., Petit, A., Dulong, C., Buquet, C., Hu, C.-Q., Mirshahi, P., Laurent, M., Fauvel-Lafève, F., Cazin, L., Vannier, J.-P., Lu, H., Soria, J., Li, H., Varin, R., Soria, C. (2013). Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines. BMC Cancer, 13, 63. [CrossRef]
• 31. Libson, S., Lippman, M. (2014). A review of clinical aspects of breast cancer. International Review of Psychiatry (Abingdon, England), 26(1), 4–15. [CrossRef]
• 32. Weigelt, B., Peterse, J. L., Van ’t Veer, L. J. (2005). Breast cancer metastasis: markers and models. Nature Reviews. Cancer, 5(8), 591–602. [CrossRef]
• 33. LaPorta, E., Welsh, J. (2014). Modeling vitamin D actions in triple negative/basal-like breast cancer. The Journal of Steroid Biochemistry and Molecular Biology, 144 Pt A, 65–73. [CrossRef]