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Yer Elması (Helianthus tuberosus L.) Ekstraktlarının Sitotoksik, Antimetastatik ve Apoptotik Aktivitelerinin Araştırılması: MCF-7 ve MCF-12A Hücrelerinin Karşılaştırılması

Year 2024, Volume: 27 Issue: 2, 293 - 303, 01.04.2024

Fadime Beyazyüz Emine Arslan Gozde Koygun

https://doi.org/10.18016/ksutarimdoga.vi.1292478

Abstract

Tamamlayıcı alternatif tıp tedavileri, daha yüksek verim, daha düşük maliyet ve yan etkilerinin minimum olması nedeniyle kanser tedavileri için daha popüler hale gelmektedir. Bu bağlamda çeşitli biyoaktif maddelerden oluşması, yüksek antioksidan aktivitesi, zengin inülin içeriği ve fonksiyonel gıda bileşenleri üretmesi nedeniyle yer elması (Helianthus tuberosus L.) önemli bir tıbbi bitkidir. Bu çalışma, yeni alternatif tıp tedavilerini keşfetmek amacıyla, yer elmasının hem kabuk hem de yumru özütünün farklı meme hücre hatları üzerinde kansere karşı etkinliğini araştırmak için yapılmıştır. Yer elmasının sitotoksik etkileri, farklı inkübasyon sürelerinde (24s,48s,72s) farklı konsantrasyonlar kullanılarak XTT yöntemi ile değerlendirilmiştir. İnvazyon, adezyon ve apoptotik çalışmalar 48 saat ve 72 saat uygulamalardan elde edilen IC50 değerlerine göre yürütülmüştür. Yer elması özütleri sağlıklı insan meme hücresi üzerinde sitotoksik aktivite göstermezken, doz ve zamana bağlı olarak tümöral hücre ölümünü indüklemiştir. Yumru ve kabuk özlerinin en etkili dozları 48 saatte sırasıyla 108.8 µM ve 134.2 µM ve 72 saatte 20 µM ve 5 µM olarak gözlenmiştir. Yer elması özleri MCF-7 hücre hatları üzerinde adezyon ve invazyonu önemli ölçüde engellemesi nedeniyle güçlü bir anti-metastatik aktivite göstermiştir. Mitokondriyal membran potansiyelini ve nükleer morfolojiyi belirlemek için sırasıyla TMRE ve AnnexinV/ 7AAD boyaması kullanıldı. Sonuçlar birbiriyle uyumlu bulundu. Literatürde bir ilk olan bu çalışma, yer elmasının hem yumru hem de kabuk özütünün anti-kanser etkinliğini ortaya koyarak meme kanseri tedavisi için önerilebilir.

Keywords

Adezyon Apoptoz İnvazyon MCF-7 hücreleri Sitotoksisite

Project Number

17201144

References

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  • Mariadoss, A.V.A., Park, S., Saravanakumar, K., Sathiyaseelan, A. & Wang, M. H. (2021). Ethyl acetate fraction of Helianthus Tuberosus L. ınduces anti-diabetic, and wound-healing activities in ınsulin-resistant human liver cancer and mouse fibroblast cells. Antioxidants; 10(1), 99, 2021.
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Investigation of Cytotoxic, Antimetastatic and Apoptotic Activities of Jerusalem Artichoke (Helianthus tuberosus L.) Extracts: Comparison with MCF-7 and MCF-12A Cells

Year 2024, Volume: 27 Issue: 2, 293 - 303, 01.04.2024

Fadime Beyazyüz Emine Arslan Gozde Koygun

https://doi.org/10.18016/ksutarimdoga.vi.1292478

Abstract

Jerusalem artichoke (Helianthus tuberosus L.) is an important medicinal plant due to its composition of several bioactive substances, high antioxidant activity, rich inulin content and produces functional food ingredients. Complementary alternative medicine therapies become more popular for cancer treatments because of higher efficiency, lower cost and minimum side effects. This study reported anti-cancer efficiency of both shell and tuber extract of Jerusalem artichoke (JA) on different breast cell lines with the purpose of discovering new alternative medicine therapies. Cytotoxic effects of JA were evaluated by XTT method by using different concentrations on different incubation times (24h, 48h and 72h). Invasion, adhesion and apoptotic studies were performed with IC50 values for 48h and 72h. JA extracts do not show cytotoxic activity on healthy human breast cell, while they induce tumoral cell death with dose and time-dependent manner. The most effective doses of tuber and shell extracts were 108.8 µM and 134.2 µM at 48h and 20 µM ve 5 µM at 72h, respectively. It demonstrated robust anti-metastatic activity on MCF-7 cell lines because it inhibited adhesion, and invasion, significantly. TMRE and AnnexinV/7AAD staining were used for determine to mitochondrial membrane potential and nuclear morphology, respectively The results were found consistent with each other. Overall, this paper which first in literature demonstrates the anti-cancer efficacy of the JA both tuber and shell extract which can be proposed as a potent candidate for the treatment of breast cancer.

Keywords

Adhesion Apoptosis Cytotoxicity Invasion MCF-7 cells

Supporting Institution

BAP

Project Number

17201144

Thanks

This research was supported by Selçuk University Scientific Research Project (BAP) (No. 17201144). This study was presented as an oral presentation 1st International Plant Biology Congress in 2018(10-12May) and published as an abstract in the congrees book. F. B and E.A. conceived the original idea and build E.A. supervised the project. The experiments were performed by F.B and G.K. I am grateful to Elif GÜLBAHÇE MUTLU for the plant collection and extraction steps of the experiment, and I would like to thank Mert SUDAĞIDAN for helping us with the devices for the experiments.

References

  • Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda, T., Ramaswamy, S. et al. (2014). Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell ; 158, 1110 –1122.
  • Afoakwah, N.A., Zhao, Y., & Dong, Y. (2023). Biological functionality and characteristics of Jerusalem artichoke (Helianthus tuberosus L.) tuber extracts. Acta Alimentaria, 52(1), 12-26.
  • Ahmed, M.S., El-Sakhawy, F.S., Soliman, S.N., & Abou-Hussein, D.M.R. (2005). Phytochemical and biological study of Helianthus tuberosus L. Egypt. J. Biomedical Scence; 18, 134–147.
  • Akhtar, K., & Rahman, M.M. (2018). Use of alternative medicine is delaying health-seeking behavior by Bangladeshi breast cancer patients. European Journal of Breast Health, 14(3), 166.
  • Amarowicz, R., Cwalina-Ambroziak, B., Janiak, M. A., & Bogucka, B. (2020). Effect of N fertilization on the content of phenolic compounds in Jerusalem artichoke (Helianthus tuberosus L.) tubers and their antioxidant capacity. Agronomy, 10(8), 1215.
  • Anderson, R.L., Balasas, T., Callaghan. J., Coombes, R.C., Evans, J., et al. (2019). A framework for the development of effective anti-metastatic agents. Nature Reviews Clinical Oncology; 16, 185–204. doi: 10.1038/s41571-018-0134-8.
  • Beşli, N., Yenmis, G., Tunçdemir, M., Sarac, E., Doğan, Y., Solakoğlu, S. & Sultuybek, G. K. (2019). Metformin suppresses the proliferation and invasion through NF-kB and MMPs in MCF-7 cell line. Turkish Journal of Biochemistry; 45(3), 295-304. DOI:10.1515/tjb-2019-0197.
  • Çakır, S., Kafadar, M. T., Arslan, Ş.N., Türkan, A., Kara, B. & İnan, A. (2016). Review of risk factors in women diagnosed with breast cancer in the light of current data. FNG & Bilim Tıp Dergisi, 186-194.
  • Çapanoğlu, G. & Bakar, E. (2018). Molecular prognostic factors in breast cancer and breast cancer metastasis, Journal of Cumhuriyet University Health Sciences Institute, 3(2), 40-48,.
  • Debela, D. T., Muzazu, S. G., Heraro, K. D., Ndalama, M. T., Mesele, B. W., Haile, D. C., ... & Manyazewal, T. (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE Open Medicine, 9, 20503121211034366.
  • Demchenko, A. P. (2013). Beyond annexin V: fluorescence response of cellular membranes to apoptosis. Cytotechnology, 65(2), 157-172.
  • Demir, T., Akpinar, Ö., Haki, K. A. R. A., & Güngör, H. (2019). Nar (Punica granatum L.) kabuğunun in vitro antidiyabetik, antienflamatuar, sitotoksik, antioksidan ve antimikrobiyal aktivitesi. Akademik Gıda, 17(1), 61-71.
  • Downey, M.O., Mazza, M. & Krstic, M.P. (2007). Development of a stable extract for anthocyanins and flavonols from grape skin. American Journal of Enology and Viticulture, 58 (3), 358-364, 2007. ISSN: 0002-9254.
  • Friedl, P. & Wolf, K. (2003). Tumour-cell invasion and migration: diversity and escape mechanisms. Nature reviews cancer, 3(5), 362-374.
  • Giammona, G., Mauro, N. & Scialabba, C. (2016). Inulin for cancer therapy: present and perspectives. International Journal. 5(1), 63-69
  • Giansanti, V. & Anna, I.S. (2008). Cell death: a one-way journey to the graveyard. The Open Biology Journal 1(1), 27-34. DOI: 10.2174/18741967008010 10027.
  • Griffaut, B., Debiton, E., Madelmont, J., Maurizis, J. & Ledoigt, G. (2007). Stressed jerusalem artichoke tubers (Helianthus tuberosus L.) excrete a protein fraction with specific cytotoxicity on plant and animal tumour cell, Biochimica et Biophysica Acta (BBA)-General Subjects; 1770 (9), 1324-1330. doi: https://doi.org/10.1016/j.bbagen.2007.06.007.
  • Gupta,D. & Chaturvedi, N. (2020). Impact of processing on inulin and sugars content of Jerusalem Artichoke Tuber. Research Journal of Pharmacy and Technology; 13, 3143–3146.
  • Hortobagyi,G. (2003). The curability of breast cancer: present and future. European J of Cancer Supplements; 1, 24–34. doi: 10.1016/S1359-6349(03)00003-
  • Iqbal, J., Abbasi, B.A., Mahmood, T., Kanwal, S., Ali, B., Shah, S.A. & Khalil, A.T. (2017). Plant-derived anticancer agents: A green anticancer approach. Asian Pacific J of Tropical Biomedicine; 7, 1129–1150.
  • Islam, M. R., Akash, S., Rahman, M. M., Nowrin, F. T., Akter, T., Shohag, S., ... & Simal-Gandara, J. (2022). Colon cancer and colorectal cancer: Prevention and treatment by potential natural products. Chemico-Biological Interactions, 110170.
  • Janiszewska, M., Primi, M.C. & Izard, T. (2020). Cell adhesion in cancer: beyond the migration of single cells. J of Biological Chemistry; 295(8), 2495-2505.
  • Kapusta, I., Krok, E., Jamro, D., Cebulak, T., Kaszuba, J. & Salach, R.T. (2013). Identification and quantification of phenolic compounds from jerusalem artichoke (Helianthus tuberosus L.) tubers. Journal of Food, Agriculture & Environment; 11(3/4), 601-606.
  • Kramer, N., Walzl, A., Unger, C., Rosner, M., Krupitza, G., Hengstschläger, M. & Dolzing, H. (2013). In vitro cell migration and invasion assays. Mutation Research/Reviews in Mutation Research; 752(1), 10–24. doi: 10.1016/j.mrrev.2012.08.001.
  • Majumder, M., Debnath, S., Gajbhiye, R.L., Saikia, R., Gogoi, B., Samanta, S.K., Das, D.K. et al. (2019). Ricinus communis L. fruit extract inhibits migration/invasion, induces apoptosis in breast cancer cells and arrests tumor progression in vivo. Scientific Reports; 9(1), 1-14. doi: https://doi.org/ 10.1038/s41598-019-50769-x.
  • Majumder, M., Sharma, M., Maiti, S. & Mukhopadhyay, R. (2020). Edible tuber amorphophallus paeoniifolius (dennst.) extract ınduces apoptosis and suppresses migration of breast cancer cells. Nutrition and Cancer; 1-14. DOI: 10.1080/01635581.2020.1830127.
  • Mariadoss, A.V.A., Park, S., Saravanakumar, K., Sathiyaseelan, A. & Wang, M. H. (2021). Ethyl acetate fraction of Helianthus Tuberosus L. ınduces anti-diabetic, and wound-healing activities in ınsulin-resistant human liver cancer and mouse fibroblast cells. Antioxidants; 10(1), 99, 2021.
  • Matissek, K.J., Mossalam, M., Okal, A. & Lim, C.S. (2013). The DNA binding domain of p53 is sufficient to trigger a potent apoptotic response at the mitochondria. Molecular Pharmacology; 10(10), 3592–3602. [PubMed: 23968395].
  • Michalska-Ciechanowska, A., Wojdyło, A., Bogucka, B. & Dubis, B. (2019). Moderation of ınulin and polyphenolics contents in three cultivars of Helianthus tuberosus L. by potassium fertilization. Agronomy; 9, 884, doi:10.3390/agronomy9120884
  • Nizioł-Łukaszewska, Z., Furman-Toczek, D. & Zagórska-Dziok, M. (2018). Antioxidant activity and cytotoxicity of Jerusalem artichoke tubers and leaves extract on HaCaT and BJ fibroblast cells. Lipids in Health and Disease; 17(1), 280. doi: https://doi.org/10.1186/s12944-018-0929-8.
  • Okal, A., Reaz, S. & Lim, C. (2013). Cancer biology: some causes for a variety of different diseases. In: Bae YH, Mrsny RJ,Park K.(editors). Cancer Targeted Drug Delivery . New York: Springer; 2013. 121-159, 2013.
  • O'Reilly, C.M., Fogarty, K.E., Drummond, R.M., Tuft, R.A., Walsh, V. & Jr, J. (2003). Quantitative analysis of spontaneous mitochondrial depolarizations. Biophys J; 85(5), 3350–3357. [PubMed: 14581236.
  • Pan, L., Sinden, M.R., Kennedy, A.H., Chai, H., Watson, L.E., Graham, T.L., & Kinghorn, A.D. (2009). Bioactive constituents of Helianthus tuberosus (Jerusalem artichoke). Phytochemistry Letters; 15-18. Doi: https://doi.org/10.1016/j.phytol. 2008.10.003.
  • Petkova, N., Ivanov, I., Denev, P., & Pavlov, A. (2014). Bioactive substance and free radical scavenging activities of flour from Jerusalem artichoke (Helianthus tuberosus L.) tubers–a comparative study, Turkish Agricultural and Natural Sci J; 1 (Special Issue:2), 1773-1778, 2014.
  • Ricci, J.E., Gottlieb, R.A. & Green, D. (2003). Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. J of Cell Biology; 160(1), 65–75.[PubMed: 12515825].
  • Roy, A. (2021). Plumbagin: a potential anti-cancer compound. Mini Reviews in Medicinal Chemistry, 21(6), 731-737.
  • Saikaew, S., Tangwongchai, R., & Sae-Eaw, A. (2010). The effect of temperature and storage time on the chemical and physical compositions changes of kaentawan (Helianthus tuberosus L.) tubers after harvesting. Agricultural Sci J; 4 (3/1), 249-252.
  • Sawicka, B., Skiba, D., Pszczó, Å.P., Aslan, I., Sharifi, J. & Krochmal-Marczak, B. (2020). Jerusalem artichoke (Helianthus tuberosus L.) as a medicinal plant and its natural products. Cellular and Molecular Bio; 66(4), 160-177.
  • Seljåsen, R. & Slimestad, R. (2005). Fructooligosaccharides and phenolics in flesh and peel of spring harvested Helianthus, SHS Acta Horticulturae 74; I International Symposium on Human Health Effects of Fruits and Vegetables.
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There are 47 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section RESEARCH ARTICLE
Authors

Fadime Beyazyüz 0000-0003-3629-0559

Emine Arslan 0000-0002-0782-506X

Gozde Koygun 0000-0003-1571-2986

Project Number 17201144
Early Pub Date January 21, 2024
Publication Date April 1, 2024
Submission Date May 5, 2023
Acceptance Date September 28, 2023
Published in Issue Year 2024Volume: 27 Issue: 2

Cite

APA Beyazyüz, F., Arslan, E., & Koygun, G. (2024). Investigation of Cytotoxic, Antimetastatic and Apoptotic Activities of Jerusalem Artichoke (Helianthus tuberosus L.) Extracts: Comparison with MCF-7 and MCF-12A Cells. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(2), 293-303. https://doi.org/10.18016/ksutarimdoga.vi.1292478
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