REAL TIME ANALYSIS OF IMPEDANCE ALTERATIONS BY THE NEUROTOXICITY OF SCOPOLETIN ON SHSY5Y NEUROBLASTOMA CELLS

Yıl 2022, Cilt: 31 Sayı: 2, 242 - 248, 11.08.2022

Ayşe Kübra KARABOĞA ARSLAN Aysun ÖKÇESİZ Leyla PAŞAYEVA

https://doi.org/10.34108/eujhs.1026861

Öz

Plant coumarins are important components of the human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. Scopoletin, a natural coumarin component has been shown to inhibit the growth of many cancer cells. In this study, the cytotoxic activity of scopoletin was studied against human neuroblastoma cells SHSY5Y. The activity of scopoletin was evaluated by Sulphorhodamine B (SRB) assay and xCELLigence system. It was demonstrated that scopoletin reduced human SHSY5Y neuroblastoma cell viability. Scopoletin inhibited the growth of the cell line and the IC50 values were 91.82 and 79.19 μM for 48 h and 72 h, respectively. The findings from this study demonstrated that the growth inhibitory and cytotoxic effects of scopoletin on SHSY5Y cells may prove essential in the development of novel treatment regimens for neuroblastoma cancer.

Anahtar Kelimeler

Cytotoxicity, scopoletin, SHSY5Y, SRB, xCELLigence

Destekleyen Kurum

Erciyes Üniversitesi

Teşekkür

The study was supported by Erciyes University Scientific Research Foundation (Project No: TCD-2019-8430).

SHSY5Y NÖROBLASTOMA HÜCRELERİNDE SKOPOLETİN NÖROTOKSİSİTESİNE BAĞLI EMPEDANS DEĞİŞİKLİKLERİNİN GERÇEK ZAMANLI ANALİZİ

Öz

Bitki kumarinleri, insan diyetinin önemli bileşenleridir ve birçoğunun kansere karşı koruyucu ve tedavi edici özelliklere sahip olduğu bilinmektedir. Doğal bir kumarin bileşeni olan skopoletinin birçok kanser hücresinin büyümesini engellediği gösterilmiştir. Bu çalışmada, insan nöroblastom hücreleri SHSY5Y'ye karşı skopoletinin sitotoksik aktivitesi incelendi. Scopoletin aktivitesi, Sulphorhodamine B (SRB) testi ve xCELLigence sistemi ile değerlendirildi. Skopoletinin insan SHSY5Y nöroblastom hücre canlılığını azalttığı gösterildi. Scopoletin hücre büyümesini inhibe etti ve IC50 değerleri 48 ve 72 saat için sırasıyla 91,82 ve 79,19 µM’dir. Bu çalışmadan elde edilen bulgular, skopoletinin SHSY5Y hücreleri üzerindeki büyüme önleyici ve sitotoksik etkilerinin, nöroblastom kanseri için yeni tedavi rejimlerinin geliştirilmesinde önemli olabileceğini kanıtladı.

Anahtar Kelimeler

Sitotoksisite, skopoletin, SH-SY5Y, SRB, xCELLigence

Kaynakça

• 1. Naz H, Tarique M, Khan P et al. Evidence of vanillin binding to CAMKIV explains the anti-cancer mechanism in human hepatic carcinoma and neuroblastoma cells. Mol Cell Biochem 2018; 438(1):35-45.
• 2. Giacoppo S, Iori R, Rollin P et al. Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment. BMC Complement Altern Med 2017; 17(1):1-10.
• 3. Jan SA, Shinwari ZK, Malik M et al. Antioxidant and anticancer activities of Brassica rapa: a review. MOJ Biol Med 2018; 3(4):175-178.
• 4. Yusefi M, Shameli K, Ali RR et al. Evaluating anticancer activity of plant-mediated synthesized iron oxide nanoparticles using Punica Granatum fruit peel extract. J Mol Struct 2020; 1204:127539.
• 5. Velsankar K, Sudhahar S, Parvathy G et al. Effect of cytotoxicity and aAntibacterial activity of biosynthesis of ZnO hexagonal shaped nanoparticles by Echinochloa frumentacea grains extract as a reducing agent. Mater Chem Phys 2020; 239:121976.
• 6. Thakur A, Singla R, Jaitak V et al. Coumarins as anticancer agents: a review on synthetic strategies, mechanism of action and SAR studies. Eur J Med Chem 2015; 101:476-495.
• 7. Yuan C, Wang MH, Wang F et al. Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer. Life Sci 2021; 270:119105.
• 8. Bhattacharyya SS, Paul S, Mandal SK et al. A synthetic coumarin (4-methyl-7 hydroxy coumarin) has anti-cancer potentials against DMBA-induced skin cancer in mice. Eur J Pharmacol 2009; 614(1-3):128-136.
• 9. Tian Q, Wang L, Sun X et al. Scopoletin exerts anticancer effects on human cervical cancer cell lines by triggering apoptosis, cell cycle arrest, inhibition of cell invasion and PI3K/AKT signalling pathway. J Buon 2019; 24(3):997-1002.
• 10. Rahman MA, Hong JS, Huh SO et al. Antiproliferative properties of Saussurea lappa Clarke root extract in SH-SY5Y neuroblastoma cells via intrinsic apoptotic pathway. Anim Cells Syst 2015; 19(2):119-126.
• 11. Hua Y, Zhou N, Zhang Z et al. Isatin inhibits the invasion and metastasis of SH‑SY5Y neuroblastoma cells in vitro and in vivo. Int J Oncol 2021; 58(1):122-132.
• 12. Kumar A, Rocke JP, Kumar BN et al. Evolving treatments in high-risk neuroblastoma. Expert Opin Orphan Drugs 2020; 8(12):497-506.
• 13. Xie HR, Hu LS, Li G et al. SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease. Chin Med J (Engl). 2010; 123:1086-1092.
• 14. RTCA SP Instrument Operator’s Manual. https://www.manualslib.com/manual/1231904/Acea-Rtca-Sp-Instrument.html (accessed on 02 April 2021).
• 15. Xing JZ, Zhu L, Jackson JA et al. Dynamic monitoring of cytotoxicity on microelectronic sensors. Chem Res Toxicol 2005; 18:154-161.
• 16. Tu Y, Cheng S, Zhang S et al. Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells. Int J Mol Med 2013; 31(1):113-119.
• 17. Li CL, Han XC, Zhang H et al. Effect of scopoletin on apoptosis and cell cycle arrest in human prostate cancer cells in vitro. Trop J Pharm Res 2015; 14(4):611-617.
• 18. Pan R, Dai Y, Yang J et al. Anti‐angiogenic potential of scopoletin is associated with the inhibition of ERK1/2 activation. Drug Dev Res 2009; 70(3):214-219.
• 19. Asgar MA, Senawong G, Sripa B et al. Scopoletin potentiates the anti-cancer effects of cisplatin against cholangiocarcinoma cell lines. Bangladesh J Pharmacol 2015; 10(1):69-77.
• 20. Pan R, Gao XH, Li Y et al. Anti-arthritic effect of scopoletin, a coumarin compound occurring in Erycibe obtusifolia Benth stems, is associated with decreased angiogenesis in synovium. Fundam Clin Pharmacol 2010; 24(4):477-90.
• 21. Cheng AS, Cheng YH, Chang TL et al. Scopoletin attenuates allergy by inhibiting Th2 cytokines production in EL-4 T cells. Food Funct 2012; 3(8):886-90.
• 22. Kim EK, Kwon KB, Shin BC et al. Scopoletin induces apoptosis in human promyeloleukemic cells, accompanied by activations of nuclear factor kappaB and caspase-3. Life Sci 2005; 77(7):824-836.
• 23. Liu XL, Zhang L, Fu XL et al. Effect of scopoletin on PC3 cell proliferation and apoptosis. Acta Pharmacol Sin 2001; 22(10):929-933.
• 24. Bhattacharyya SS, Paul S, Dutta S et al. Anti-oncogenic potentials of a plant coumarin (7-hydroxy-6-methoxy coumarin) against 7, 12-dimethylbenz (a) anthracene-induced skin papilloma in mice: the possible role of several key signal proteins. Zhong Xi Yi Jie He Xue Bao 2010; 8(7):645-654.
• 25. Li L, Zhao P, Hu J et al. Synthesis, in vitro and in vivo antitumor activity of scopoletin-cinnamic acid hybrids Eur J Med Chem. 2015; 93:300-307.
• 26. Shi W, Hu J, Bao N et al. Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids. Bioorg Med Chem Lett 2017; 27(2):147-151.
• 27. Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 2006; 1:1112-1116.
• 28. Skehan P, Storeng R, Scudiero D et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990; 82:1107-1112.
• 29. RTCA Software Manual Software Version 1.2. http://www.cytometrie-imagerie-saint-antoine.org/media/4140/RTCA%201.2%20Software%20Manual.pdf (accessed on 02 April 2021).
• 30. Karaboğa Arslan AK, Yerer MB. α-Chaconine and α-Solanine inhibit RL95-2 endometrium cancer cell proliferation by reducing expression of Akt (Ser473) and ERα (Ser167). Nutrients 2018; 10(6):672.
• 31. Yuan C, Wang MH, Wang F et al. Network pharmacology and molecular docking reveal the mechanism of scopoletin against non-small cell lung cancer. Life Sci 2021; 270, 119105.
• 32. Zhao P, Dou Y, Chen L et al. SC-III3, a novel scopoletin derivative, induces autophagy of human hepatoma HepG2 cells through AMPK/mTOR signaling pathway by acting on mitochondria. Fitoterapia, 2015; 104:31-40.
• 33. Yu N, Li N, Wang K et al. Design, synthesis and biological activity evaluation of novel scopoletin-NO donor derivatives against MCF-7 human breast cancer in vitro and in vivo. Eur J Med Chem 2021; 224:113701.
• 34. Parama D, Girisa S, Khatoon E et al. An overview of the pharmacological activities of scopoletin against different chronic diseases. Pharm Res, 2022; 106202.
• 35. Pruccoli L. Neuroprotective effects of coumarins in neurodegenerative disease models. 2019. Doktora tezi, Alma Mater Studiorum University of Bologna. Farmakolojik ve Toksikolojik Bilimlerde Doktora, Gelişim ve İnsan Hareketi 10.48676/unibo/amsdottorato/8975.
• 36. Narasimhan KKS, Jayakumar D, Velusamy P et al. Morinda citrifolia and its active principle scopoletin mitigate protein aggregation and neuronal apoptosis through augmenting the DJ-1/Nrf2/ARE signaling pathway. Oxid Med Cell Longevity, 2019; 2761041.