Elektroporasyonun MCF-7 kanser hücrelerinde 4-aminopirimidin-2- (1H)-on ana maddesinden sentezlenen ligand ile Kobalt (II) ve Rutenyum (II) komplekslerinin sitotoksisiteleri üzerindeki etkisi

Giriş: Kanser komplike bir hastalıktır ve dünya çapında ölüm nedenleri arasında ilk sıralarda yer almaktadır.Elektrokemoterapi (ECT), ilaçların hücrelere girişini kolaylaştırmak için kemoterapi ve elektroporasyonun (EP) birliktekullanıldığı lokal bir tedavi yöntemidir. Bu çalışmanın amacı, sitozin ana maddesinden sentezlenmiş ligand ile onunkobalt ve rutenyum komplekslerinin MCF-7 kanser hücreleri ve L-929 sağlıklı hücrelerdeki sitotoksisitelerini incelemekve EP'nin bu bileşiklerin antikanser aktiviteleri üzerindeki etkilerini belirlemektir. Yöntemler: Bu çalışmada ilk olarak, ligand ile kobalt (Co) ve rutenyum (Ru) komplekslerinin sitotoksik aktiviteleri MCF 7 kanser hücreleri ve L-929 sağlıklı hücrelere karşı incelendi. Daha sonra, EP'nin bu bileşiklerin antikanser aktiviteleriüzerindeki etkileri MCF-7 kanser hücrelerinde belirlendi. Bileşiklerin sitotoksisite aktiviteleri MTT canlılık testi iledeğerlendirildi. Bulgular: Co(II) ve Ru(II) bileşikleri, MCF-7 kanser hücrelerine karşı iyi sitotoksisite gösterirken, L-929 sağlıklı hücrelerekarşı düşük sitotoksisite sergilediler. EP, bileşiklerin sitotoksisitesini önemli ölçüde artırdı (p

Effects of electroporation on cytotoxicity of 4-aminopyrimidin-2- (1H)-one based ligand and its Cobalt (II) and Ruthenium (II)complexes in MCF-7 cancer cells

Objective: The aim of this study was to investigate the underlying causes of obstetrical disseminated intravascular coagulation (DIC) Objective: Cancer is a complicated disease and ranks near the top among the causes of death across the world. Electrochemotherapy (ECT) is a local treatment method in which chemotherapy and electroporation (EP) are used in combination to facilitate the entry of drugs into cells. The purpose of the study is to examine the cytotoxicity of the cytosine-based ligand and its cobalt and ruthenium complexes in MCF-7 cancer cells and L-929 healthy cells, and to determine the effects of EP on the anticancer activities of these compounds.Methods: In the present study, firstly, the cytotoxic activities of the ligand and its cobalt (Co) and ruthenium (Ru) complexes were examined against MCF-7 cancer cells and L-929 healthy cells. Then, the effects of EP on the anticancer activities of these compounds were examined in MCF-7 cancer cells. Cytotoxicity activities of the compounds were determined by MTT viability test. Results: Co(II) and Ru(II) compounds showed the best cytotoxicity against MCF-7 cancer cells, while they displayed low cytotoxicity against the L-929 healthy cells. EP increased the cytotoxicity of the compounds significantly (p

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1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68: 394-424.
2. Levitsky DO, Dembitsky VM. Anti-breast cancer agents derived from plants. Nat Products Bioprospect. 2014; 5: 1–16.
3. Michel O, Kulbacka J, Saczko J, et al. Electroporation with cisplatin against metastatic pancreatic cancer: In Vitro Study on human primary cell culture. Biomed Res Int. 2018; 2018: 1–12.
4. Çı̇ftcı̇ F. The role of breast-conserving surgery in the treatment of early-stage breast cancer. Dicle Med J. 2020; 852–8.
5. Housman G, Byler S, Heerboth S, et al. Drug resistance in cancer: an overview. Cancers (Basel). 2014; 6: 1769–92.
6. Ramesh G, Daravath S, Ganji N, et al. Facile synthesis, structural characterization, DNA binding, incision evaluation, antioxidant and antimicrobial activity studies of Cobalt (II), Nickle (II) and Copper (II) complexes of 3-amino-5-(4-fluorophenyl) isoxazole derivatives. J Mol Struct. 2020; 1202: 127338.
7. Thamilarasan V, Sengottuvelan N, Sudha A, Srinivasan P, Chakkaravarthi G. Cobalt (III) complexes as potential anticancer agents: Physicochemical, structural, cytotoxic activity and DNA/protein interactions. J Photochem Photobiol B. 2016; 162: 558–69.
8. Motswainyana WM, Ajibade PA. Anticancer activities of mononuclear ruthenium(II) coordination complexes. Adv Chem. 2015; 2015: 1– 21.
9. Zhu J, Wang F, Liu X, Tan L. Stabilization of an intermolecular RNA triplex by two novel binders Lys- and Arg-rich Ru(II) polypyridyl metallopeptides. J Inorg Biochem. 2020; 210: 111171.
10. Thota S, Rodrigues DA, Crans DC, Barreiro EJ. Ru (II) Compounds: Next-Generation Anticancer Metallotherapeutics? J Med Chem. 2018; 61: 5805– 5821.
11. Clover AJP, Salwa SP, Bourke MG, et al. Electrochemotherapy for the treatment of primary basal cell carcinoma; A randomised control trial comparing electrochemotherapy and surgery with five year follow up. Eur J Surg Oncol. 2020; 46: 847– 54.
12. Probst U, Fuhrmann I, Beyer L, Wiggermann P. Electrochemotherapy as a new modality in interventional oncology: A review. Technol Cancer Res Treat. 2018; 17: 153303381878532.
13. Alkış ME, Keleştemür Ü, Alan Y, Turan N, Buldurun K. Cobalt and ruthenium complexes with pyrimidine based schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency. J Mol Struct. 2021; 1226: 129402.
14. Alkış ME, Buldurun K, Turan N, et al. Synthesis, characterization, antiproliferative of pyrimidine based ligand and its Ni(II) and Pd(II) complexes and effectiveness of electroporation. J Biomol Struct Dyn. 2020; 1–11.
15. Campana LG, Miklavčič D, Bertino G, et al. Electrochemotherapy of superficial tumors - Current status: Basic principles, operating procedures, shared indications, and emerging applications. Semin Oncol. 2019; 46: 173–91.
16. Kenny RG, Marmion CJ. Toward multi-targeted platinum and ruthenium drugs—A new paradigm in cancer drug treatment regimens? Chem Rev. 2019; 119: 1058–137.
17. Munteanu CR, Suntharalingam K. Advances in cobalt complexes as anticancer agents. Dalton Transactions. 2015; 44: 13796–808.
18. Zheng W, Zhao Y, Luo Q, et al. Rational design of multi-targeting ruthenium- and platinum-based anticancer complexes. Science China Chemistry. 2016; 59: 1240–9.
19. Da Silva MM, Camargo MS, Correa RS, et al. Nonmutagenic Ru (II) complexes: cytotoxicity, topoisomerase IB inhibition, DNA and HSA binding. Dalton Transactions. 2019; 48: 14885–97.
20. Iida J, Bell-Loncella ET, Purazo ML, et al. Inhibition of cancer cell growth by ruthenium complexes. J Transl Med. 2016; 14: 48.
21. Dhahagani K, Mathan Kumar S, Chakkaravarthi G, et al. Synthesis and spectral characterization of Schiff base complexes of Cu (II), Co (II), Zn (II) and VO (IV) containing 4-(4-aminophenyl) morpholine derivatives: Antimicrobial evaluation and anticancer studies. Spectrochim Acta A Mol Biomol Spectrosc. 2014; 117: 87–94.
22. Martinez-Bulit P, Garza-Ortíz A, Mijangos E, et al. 2,6-Bis(2,6-diethyl phenylimino methyl) pyridine coordination compounds with cobalt (II), nickel (II), copper (II), and zinc (II): synthesis, spectroscopic characterization, X-ray study and in vitro cytotoxicity. J Inorg Biochem. 2015; 142: 1–7.
23. Ritacco I, Russo N, Sicilia E. DFT investigation of the mechanism of action of organoiridium(III) complexes as anticancer agents. Inorg Chem. 2015; 54: 10801–10.
24. Fiorentzis M, Kalirai H, Katopodis P, et al. Electrochemotherapy with bleomycin and cisplatin enhances cytotoxicity in primary and metastatic uveal melanoma cell lines in vitro. Neoplasma. 2018; 65: 210–5.
25. Schmidt G, Juhasz-Böss I, Solomayer E-F, Herr D. Electrochemotherapy in breast cancer: A review of references. Geburtshilfe Frauenheilkd. 2014; 74: 557–62.
26. Wichtowski M, Murawa D, Czarnecki R, et al. Electrochemotherapy in the Treatment of Breast Cancer Metastasis to the Skin and Subcutaneous Tissue - Multicenter Experience. Oncol Res Treat. 2018; 42: 47–51.
27. Esmekaya MA, Kayhan H, Yagci M, Coskun A, Canseven AG. Effects of electroporation on tamoxifen delivery in estrogen receptor positive (ER+) human breast carcinoma cells. Cell Biochem Biophys. 2017; 75: 103–9.
28. Mittal L, Aryal UK, Camarillo IG, Raman V, Sundararajan R. Effective electrochemotherapy with curcumin in MDA-MB-231-human, triple negative breast cancer cells: A global proteomics study. Bioelectrochemistry. 2020; 131: 107350.
29. Esmaeili N, Friebe M. Electrochemotherapy: A review of current status, alternative IGP approaches, and future perspectives. J Healthc Eng. 2019; 2019: 1–11
30. Frandsen SK, McNeil AK, Novak I, McNeil PL, Gehl J. Difference in membrane repair capacity between cancer cell lines and a normal cell line. J Membr Biol. 2016; 249: 569–76.