Nazlı Savlak, Mustafa Soyöz, İbrahim Pirim, Burcu Çerçi, Melek Pehlivan, Hatice İlayhan Karahan Çöven, Aslı Eldem, Tuba Öz

The Cytotoxic Effect of Polygonium cognatum and Chemotherapeutic Effect of Doxorubicin on Glioblastoma Cells

Objective: Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor common in adults. Owing to the present difficulty in treating GBM, developing alternative methods is of utmost importance. Recently, the efficacy of various plant extractsin cancer treatment have been evaluated. Polygonum cognatum (P. cognatum) known as ‘Madımak’ is used in herbal medicine inTurkey.Methods: In this study, we investigated the cytotoxity of P. cognatum in the treatment of glioblastoma and its contribution to theeffectiveness of doxorubicin (DXR). In the U87 cell line of the P. cognatum and doxorubicin administered at different doses, IC50doses were determined using the 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT) method andthe effects of combined administration at these doses were examined (respectively 10–125 µg/ml and 0.1–10 µg/ml at 24, 48, and72 h).Results: P. cognatum extract decreased the cell viability of U87 cells in a time and concentration-dependent manner. It also increased the apoptotic effectiveness of DXR in U87 cells.Conclusion: This is the first preliminary study that investigates the treatment of P. cognatum on glioblastoma in vitro. Further studies are required to investigate the effect of the extract on healthy human cells and to understand signaling pathways.

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1. Urbańska K, Sokołowska J, Szmidt M, Sysa P. Glioblastoma multiforme - an overview. Contemp Oncol 2014; 18: 307-12. [Crossref]
2. Zhang P, Sun S, Li N, Ho A, Kiang K, Zhang X, et al. Rutin increases the cytotoxicity of temozolomide in glioblastoma via autophagy inhibition. J Neurooncol 2017; 132: 393-400. [Crossref]
3. Malinovskaya Y, Melnikov P, Baklaushe, V, Gabashvili A, Osipova N, Mantrov S, et al. Delivery of doxorubicin-loaded PLGA nanoparticles into U87 human glioblastoma cells. Int J Pharm 2017; 524: 77‐90. [Crossref]
4. Ngulde SI, Sandabe UK, Abounader R, Dawson TK, Zhang Y, Iliya I, et al. Ethanol Extract of Securidaca longipedunculata Induces Apoptosis in Brain Tumor (U87) Cells. Biomed Res Int 2019; 2019: 1-5. [Crossref]
5. Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther 2014; 10: 853-8. [Crossref]
6. Yang F, Teves SS, Kemp CJ, Henikoff S. Doxorubicin, DNA torsion, and chromatin dynamics. Biochim Biophys Acta 2014; 1845: 84-9. [Crossref]
7. Hau P, Fabel K, Baumgart U, Rümmele P, Grauer O, Bock A, et al. Pegylated liposomal doxorubicin-efficacy in patients with recurrent high-grade glioma. Cancer 2004; 100: 1199-207. [Crossref]
8. Zou D, Wang W, Lei D, Yin Y, Ren P, Chen J, et al. Penetration of bloodbrain bar-rier and antitumor activity and nerve repair in glioma by doxorubicin loaded monosialoganglioside micelles system. Int J Nanomedicine 2017; 12: 4879-89. [Crossref]
9. Meng L, Chu X, Xing H, Liu X, Xin X, Chen L, et al. Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol. Int J Pharm 2019; 567: 118485. [Crossref]
10. Adem FA, Mbaveng AT, Kuete V, Heydenreich M, Ndakala A, Irungu B, et al. Cytotoxicity of isoflavones and biflavonoids from Ormocarpum kirkii towards multi-factorial drug resistant cancer. Phytomedicine 2019; 58: 152853. [Crossref]
11. Rezadoost MH, Kumleh HH, Ghasempour A. Cytotoxicity and apoptosis induction in breast cancer, skin cancer and glioblastoma cells by plant extracts. Mol Biol Rep 2019; 46: 5131-42. [Crossref]
12. Mulpur BH, Nabors LB, Thompson RC, Olson JJ, LaRocca RV, Thompson Z, et al. Complementary therapy and survival in glioblastoma. Neurooncol Pract 2015; 2: 122-6. [Crossref]
13. Önen H, Altuntaş E, Özgöz E, Bayram M, Özcan S. Moisture effect on physical properties of knotweed (Polygonum cognatum Meissn.) seeds. Journal of Agricultural Faculty of Gaziosmanpasa University 2014; 31: 15-24. [Crossref]
14. Baytop T. Therapy with Medicinal Plants in Turkey Past and Present. 2th ed. Istanbul: Nobel Tip Kitabevi;1999.
15. Kanthal L, Dey A, Satyavathi K, Bhojaraju P. GC-MS analysis of bioactive compounds in methanolic extract of Lactuca runcinata DC. Pharmacognosy Res 2014; 6: 58-61. [Crossref]
16. Yool AJ, Ramesh S. Molecular Targets for Combined Therapeutic Strategies to Limit Glioblastoma Cell Migration and Invasion. Front Pharmacol 2020; 11: 1-26. [Crossref]
17. Carter TC, Medina-Flores R, Lawler BE. Glioblastoma Treatment with Temozolomide and Bevacizumab and Overall Survival in a Rural Tertiary Healthcare Practice. Biomed Res Int 2018; 6204676: 1-10. [Crossref]
18. Stupp R, Mason WP, Van Den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352: 987-96. [Crossref]
19. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352: 997-1003. [Crossref]
20. Ramirez Y, Weatherbee J, Wheelhouse R, Ross A. Glioblastoma Multiforme Therapy and Mechanisms of Resistance. Pharmaceuticals 2013; 6: 1475-506. [Crossref]
21. Eom YW, Kim MA, Park SXS, Goo MJ, Kwon HJ, Sohn S, et al. Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 2005; 24: 4765-77. [Crossref]
22. Lesniak MS, Upadhyay U, Goodwin R, Tyler B, Brem H. Local delivery of doxorubicin for the treatment of malignant brain tumors in rats. Anticancer Res 2005; 25: 3825-31.
23. Hui A, Prakash O. Doxorubicin Response to Temozolomide-resistant Brain Cancer Glioblastoma Cells. Louisiana Cancer Research Consortium, New Orleans. 2015. Available from: https://www.medschool. lsuhsc.edu/cancer_center/docs/Hui%2036x60%20-%20Closing%20Poster%20(STREC2015).pdf
24. Wang CW, Chen CL, Wang CK, Chang YJ, Jian JY, Lin CS, et al. Cisplatin-, doxorubicin-, and docetaxel-induced cell death promoted by the aqueous extract of solanum nigrum in human ovarian carcinoma cells. Integr Cancer Ther 2015; 14: 546-55. [Crossref]
25. Yu J, Wang C, Kong Q, Wu X, Lu JJ, Chen X. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine 2018; 40: 125-39. [Crossref]
26. Wang L, Sun J, Gao P, Su K, Wu H, Li J, et al. Wnt1-inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway. J Cell Physiol 2019; 234: 15941-50. [Crossref]
27. To KKW, Wu X, Yin C, Chai S, Yao S, Kadioglu O, et al. Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes. J Ethnopharmacol 2017; 203: 110-9. [Crossref]
28. Saraç H, Daştan T, Demirbaş A, Durna Daştan S, Karaköy T, Durukan H. Madımak (Polygonum cognatum Meissn.) Bitki Özütlerinin Besin Elementleri ve In vitro Antikanserojen Aktiviteleri Yönünden Değerlendirilmesi, Süleyman Demirel Üniversitesi Ziraat Fakültesi Dergisi 1. Uluslararası Tarımsal Yapılar ve Sulama Kongresi Özel Sayısı 2018; 340-7.
29. Eruygur N, Ucar E, Ataş M, Ergul M, Ergul M, Sozmen F. Determination of biological activity of Tragopogon porrifolius and Polygonum cognatum consumed intensively by people in Sivas. Toxicol Rep 2020; 7: 59-66. [Crossref]
30. Pekdemir S, Çiftci M, Karatepe M. Elazığ’da Yetişen Polygonum cognatum Meissn (Madımak) Bitki Ekstraktlarının In vitro Biyolojik Aktiviteleri ve Bazı Fitokimyasal Fitokimyasal Bileşileşenlerinin Belirlenmesi. Avrupa Bilim ve Teknoloji Dergisi 2020;18: 368-78. [Crossref]