Selenyum Dioksit ve Paklitaksel Kombinasyonunun MDA-MB-231 Meme Kanseri Hücre Hattı Üzerine Etkisinin Değerlendirilmesi

Amaç: Bu çalışmanın amacı, bitkisel kökenli bileşik olan selenyum dioksit (SEL) ile kemoterapötik ilaç olan paklitaksel’in (PTX) kombine uygulamasının MDA-MB-231 meme kanseri hücre hattı üzerine etkisinin belirlenmesidir. Gereç ve Yöntemler: Çalışmamızda öncelikle SEL’in yarı maksimal inhibitör konsantrasyonunun belirlenmesi amacıyla MTT testi yapıldı. Deney grupları SEL1, SEL2, SEL3, PTX, SEL1+PTX, SEL2+PTX ve SEL3+PTX şeklinde oluşturulduktan sonra apoptoz TUNEL metodu, NF-kB ekspresyonu immunofloresan boyama metodu ile hücre canlılığı ise MTT analizi ile gösterildi. Bulgular: SEL’in meme kanseri hücrelerinde hücre canlılığını azalttığı gösterildi. SEL1, SEL2, SEL3, PTX gruplarında kontrole göre apoptozun arttığı görüldü (p<0,001, p<0,001, p=0,312, p<0,001). SEL1+PTX, SEL2+PTX ve SEL3+PTX gruplarında ise PTX grubuna göre apoptozun azaldığı belirlendi (p=0,009, p=0,011, p=0,010). SEL1, SEL2, SEL3, PTX gruplarında kontrole göre NF-kB immünreaktivite yoğunluğunda azalma olduğu görüldü (p<0,001, p=0,002, p>0,999, p<0,001). SEL1+PTX, SEL2+PTX ve SEL3+PTX gruplarında NF-kB ekspresyonunda PTX grubuna göre artış olduğu belirlendi (p>0,999, p>0,999, p>0,999). SEL1+PTX, SEL2+PTX ve SEL3+PTX gruplarında PTX grubuna göre hücre canlılığında istatistiksel olarak anlamlı olmayan bir artış olduğu görüldü (p>0,999, p>0,999, p=0,725). Sonuç: Mevcut çalışmada MDA-MB-231 meme kanseri hücre dizisinde SEL ve PTX’in antagonistik etkiye sahip oldukları belirlenmiştir.

Anahtar Kelimeler:

apoptoz, MDA-MB-231, NF-kβ, Paklitaksel, Selenyum dioksit

Evaluation of the Effect of Selenium Dioxide and Paclitaxel Combination on MDA-MB-231 Breast Cancer Cell Line

Aim: The aim of this study is to determine the effect of the combined application of the plant-derived compound selenium dioxide and the chemotherapeutic drug paclitaxel (PTX) on the MDA-MB-231 breast cancer cell line. Material and methods: In our study, first of all, the MTT test was performed to determine the semi-maximal inhibitory concentration of selenium dioxide. After the experimental groups were formed as SEL1, SEL2, SEL3, PTX, SEL1+PTX, SEL2+PTX, and SEL3+PTX, apoptosis was demonstrated by the TUNEL method, NF-kB expression was demonstrated by the immunofluorescent staining method, and cell viability was demonstrated by MTT analysis. Results: Selenium dioxide has been shown to decrease cell viability in breast cancer cells. Apoptosis was observed to be increased in SEL1, SEL2, SEL3, and PTX groups compared to control(p<0.001, p<0.001, p=0.312, p<0.001). It was determined that apoptosis was decreased in the SEL1+PTX, SEL2+PTX and SEL3+PTX groups compared to the PTX group (p=0.009, p=0.011, p=0.010). A decrease in NF-kB immunoreactivity intensity was observed in the SEL1, SEL2, SEL3, PTX groups compared to the control (p<0.001, p=0.002, p>0.999, p<0.001). It was determined that there was an increase in NF-kB expression in the SEL1+PTX, SEL2+PTX and SEL3+PTX groups compared to the PTX group (p>0.999, p>0.999, p>0.999). There was a statistically insignificant increase in cell viability in the SEL1+PTX, SEL2+PTX, and SEL3+PTX groups compared to the PTX group. Conclusion: In the current study, it was determined that SEL and PTX have antagonistic effects on the MDA-MB-231 breast cancer cell line.

Keywords:

Apoptosis, MDA-MB-231, NF-kβ, Paclitaxel, Selenium dioxide,

PDF

___

World healt organization. https://www.who.int/news-room/fact-sheets/detail/breast-cancer (Erişim tarihi: 02.11.2022).
Saurel CA, Patel TA, Perez EA. Changes to adjuvant systemic therapy in breast cancer: a decade in review. Breast Cancer. 2010; 10: 196-208.
Karlığa B, Talınlı N. 3'-N-Tiyokarbamat paklitaksel türevlerinin sentezi ve biyolojik aktivite çalışmaları. Fen Bilimleri GTÜ Dergisi. 2004; 2(1): 25-30.
Torres K, Horwitz SB. Mechanisms of taxol-induced cell death are concentration dependent. Cancer Research. 1998; 58: 3620-6.
Jordan MA, Wendell K, Gardiner S, Derry WB, Copp H, Wilson L. Mitotic block induced in HeLa cells by low concentrations of Paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Research. 1996; 53: 816-25.
Frederiks C, Lam S, Guchelaar H, Boven E. Genetic polymorphisms and paclitaxel-or docetaxel-induced toxicities: a systematic review. Cancer Treatment Reviews. 2015; 41: 935-50.
Nemcova-Fürstova V, Kopperova D, Balusikova K, Ehrlichova M, Brynychova V, Vaclavikova R, et al. Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters. Toxicology and Applied Pharmacology. 2016; 310: 215-28.
Chavoshi H, Vahedian V, Saghaei S, Pirouzpanah MB, Raeisi M, Samadi N. Adjuvant therapy with silibinin ımproves the efficacy of paclitaxel and cisplatin in mcf-7 breast cancer cells. Asian Pacific Journal of Cancer Prevention. 2017; 18: 2243- 7.
Chen NC, Chyau CC, Lee YJ, Tseng HC, Chou FP. Promotion of mitotic catastrophe via activation of PTEN by paclitaxel with supplement of mulberry water extract in bladder cancer cells. Science Reports. 2016; 6: 20417.
Jiang Q, Yang M, Qu Z, Zhou J, Zhang Q. Resveratrol enhances anticancer effects of paclitaxel in HepG2 human liver cancer cells. BMC Complementary and Alternative Medicine. 2017; 17: 477.
Wilber CG. Toxicology of Se: A Review. Clin. Toxicol. 1980; 17: 171-230.
Schomburg L, Schweizer U, Köhrle J. Selenium and selenoproteins in mammals: extraordinary, essential, enigmatic. Cell Mol Life Sci. 2004; 61(16): 1988-95.
Letavayova L, Vlckova V, Brozmanova J. Selenium: from cancer prevention to DNA damage. Toxicology 2006; 227: 1-14.
Fujieda M, Naruse K, Hamauzu T, Miyazaki E, Hayashi Y, Enomoto R, et al. Effect of selenium on Cisplatin-induced nephrotoxicity in rats. Nephron Exp Nephrol 2006; 104: e112-22.
Francescato HD, Costa RS, Rodrigues Camargo SM, Zanetti MA, Lavrador MA, Bianchi MD. Effect of oral selenium administration on cisplatin-induced nephrotoxicity in rats. Pharmacol Res 2001; 43: 77-82.
Tang HL, Yuen KL, Tang HM, Fung MC. Reversibility of apoptosis in cancercells. British Journal of Cancer, 2009; 100: 118-22.
El-Bayoumy K, Sinha R. Mechanisms of mammary cancer chemoprevention by organoselenium compounds. Mutat Res. 2004; 551: 181-97.
Kierszenbaum AL. Histoloji ve Hücre Biyolojisi. Prof.Dr.Ramazan Demir, Palme Yayıncılık, Ankara, 2006, 600.
Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin, 2005; 55: 178-94.
Aggarwal Bb. Nuclear factor-kappab: The Enemy Within. Cancer Cell. 2004; 6: 203-208.
Kaltschmıdt B, Kaltschmıdt C, Hofmann Tg, Hehner Sp, Droge W, Schmıtz Ml. The Pro-or anti-apoptotic function of nf-kappab is determined by the nature of the apoptotic stimulus. Eur J Biochem. 2000; 267(12): 3828-35.
Kuppusamy UR, Wan YP, Kanthimathi MS. A comparison between selenium dioxide and selenium methionine induced cytotoxicity in estrogen receptor negative and positive breast cancer cell lines. Journal of Food Technology. 2005; 3(3): 280-3.
Sprouse AA, Herbert BS. Resveratrol augments paclitaxel treatment in MDA-MB-231 and paclitaxel-resistant MDA-MB-231 breast cancer cells. Anticancer Res. 2014; 34: 5363-74.
Tinghua Xu, Pengxi Liu, Qingming Li, Changbin Shi, Xinjie Wang. Inhibitory effects of everolimus in combination with paclitaxel on adriamycin-resistant breast cancer cell line MDA-MB-231. Taiwanese Journal of Obstetrics and Gynecology. 2020; 59(6): 828-34.
Zhang L, Wu C, Mu S, Xue W, Ma D. A chemotherapeutic self-sensibilized drug carrier delivering paclitaxel for the enhanced chemotherapy to human breast MDA-MB-231 cells. Colloids and Surfaces B: Biointerfaces. 2019; 181: 902-9.
Yerlikaya S, Zengin G, Mollica A, Baloglu MC, Celik-Altunoglu Y, Aktumsek A. A Multidirectional perspective for novel functional products: ın vitro pharmacological activities and in silico studies on ononis natrix subsp. hispanica. Frontiers in Pharmacology. 2017; 8: 600.
Baran M, Ozturk F, Canoz O, Onder GO, Yay A. The effects of apoptosis and apelin on lymph node metastasis in invasive breast carcinomas. Clinical and Experimental Medicine. 2020; 20: 507-14.
Nabekura T. Overcoming multidrug resistance in human cancer cells by natural Compounds. Toxins. 2010; 2(6): 1207-24.
Alaejos MS, Romero FRD, Romero CD. Selenium and cancer: some nutritional aspects. Nutrition 2000; 16: 376-83.
Watrach AM, Milner JA, Watrach MA, Poirier KA. Inhibition of human breast cancer cells by selenium. Cancer Lett. 1984; 25: 41-7.
Azrak RG, Frank CL, Ling X, Slocum HK, Li F, Foster BA, et al. The mechanism of methylselenocysteine and docetaxel synergistic activity in prostate cancer cells, Mol Cancer Ther 2006; 5: 2540-8.
Freitas M, Alves V, Sarmento-Ribeiro AB, Mota-Pinto A. Combined effect of sodium selenite and docetaxel on PC3 metastatic prostate cancer cell line. Biochem Biophys Res Commun. 201; 408(4): 713-9.
Aggarwal Bb. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004; 6: 203–8.
Ryan Km, Ernst MK, Rıce NR, Vousden KH. Role of NF-kappaB in p53-mediated programmed cell death. Nature. 2000; 404: 892-7.
Stark LA, Reid K, Sansom OJ, Dın FV, Guıchard S, Mayer I, et al. Aspirin activates the NF-κB signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer. Carcinogenesis, 2007; 28 (5): 968-76.
Davis JN, Kucuk O, Sarkar FH. Genistein ınhibits nf-kb activation in prostate cancer cells, Nutrition and Cancer. 1999; 35(2), 167-74.
Çelik E. Apoptotic and anti-inflammatory effects of hypericum perforatum extract in human basal cell carcinoma TE 354.T cell line. Dicle Med J. 2021; 48(1): 92-8.
Wang G, Li J, Zhang L, Huang S, Zhao X, Zhao X. Celecoxib induced apoptosis against different breast cancer cell lines by down-regulated NF-kB pathway. Biochemical and Biophysical Research Communications. 2017; 490: 969-76.