ARCTİUM MİNUS METANOL EKSTRESİNİN ÇEŞİTLİ KANSER HÜCRE HATLARI ÜZERİNDE SİTOTOKSİK ETKİLERİ
Yıl 2022,
, 742 - 754, 30.09.2022
Ayşe Arzu Şakul
,
Yasemin Yozgat Byrne
,
Ayşe Esra Karadağ
,
Ebrar Altınalan
,
Şeyma Çimen
,
Mehmet Evren Okur
Öz
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.
Destekleyen Kurum
İstanbul Medipol Üniversitesi
Kaynakça
- 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]
CYTOTOXIC EFFECTS OF ARCTIUM MINUS METHANOL EXTRACT ON VARIOUS CANCER CELL LINES
Yıl 2022,
, 742 - 754, 30.09.2022
Ayşe Arzu Şakul
,
Yasemin Yozgat Byrne
,
Ayşe Esra Karadağ
,
Ebrar Altınalan
,
Şeyma Çimen
,
Mehmet Evren Okur
Öz
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.
Kaynakça
- 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]