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Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Regulatory Effects of the Silymarin on Expression of OCT4, NANOG, and P53 in MCF7 Cell Lines

Author(s): Mohammad Reza Hajizadeh, Faezeh Esmaeili Ranjbar, Ali Abasi, Mitra Abbasifard, Mehdi Mahmoodi and Mojgan Noroozi-Karimabad*

Volume 20, Issue 4, 2024

Published on: 09 October, 2023

Article ID: e160823219846 Pages: 6

DOI: 10.2174/1573407219666230816141715

Price: $65

Abstract

Background: Breast cancer was known as the second most common cause of death in the world, natural sources compound derived from milk thistle called silymarin had already shown anticancer properties.

Objective: In the present study, silymarin was used to treat MCF7 cells and inhibition of stem cell pluripotency genes, as well as cell proliferation.

Methods: MCF7 cells were cultured in the presence of RPMI-1640 medium consisting of various silymarin extract concentrations (10, 100, 500, 1000, 2000, 3000, 4000, and 5000 μg/mL) for 24, 48, and 72 hours. The inhibitory effects of the compound on cellular proliferation were assessed via employing MTT assay techniques. Following confirming apoptosis, the fold changes of OCT4, NANOG and P53 expression were determined by quantitative Real-time PCR.

Results: There was a significant difference (p value <0.05) in cell viability when various concentrations of silymarin extract were used for 24, 48, and 72 h in comparison to the control. Real-time- PCR analysis indicated that the expression of OCT4 and NANOG was downregulated while P53 upregulated in compare to untreated control cells (p value <0.05).

Conclusion: According to these findings, the silymarin effects on MCF7 cell line and act via modulating OCT4, NANOG, and P53 pathway mediators. Silymarin may introduce this compound as a promising therapeutic compound against MCF7.

Graphical Abstract

[1]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piٌñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 2019, 144(8), 1941-1953.
[http://dx.doi.org/10.1002/ijc.31937] [PMID: 30350310]
[2]
Dean, M.; Lou, H. Genetics and genomics of prostate cancer. Asian J. Androl., 2013, 15(3), 309-313.
[http://dx.doi.org/10.1038/aja.2013.29] [PMID: 23564043]
[3]
Lee, S.Y.; Jeong, S.H.; Kim, Y.N.; Kim, J.; Kang, D.R.; Kim, H.C.; Nam, C.M. Cost-effective mammography screening in Korea: High incidence of breast cancer in young women. Cancer Sci., 2009, 100(6), 1105-1111.
[http://dx.doi.org/10.1111/j.1349-7006.2009.01147.x] [PMID: 19320639]
[4]
Reis, D.; Jones, T. Aromatherapy: Using Essential Oils as a Supportive Therapy. Clin. J. Oncol. Nurs., 2017, 21(1), 16-19.
[http://dx.doi.org/10.1188/17.CJON.16-19] [PMID: 28107335]
[5]
Gioti, K.; Tenta, R. Bioactive natural products against prostate cancer: Mechanism of action and autophagic/apoptotic molecular pathways. Planta Med., 2015, 81(7), 543-562.
[http://dx.doi.org/10.1055/s-0035-1545845] [PMID: 25875508]
[6]
Sávio, A.L.V.; da Silva, G.N.; Salvadori, D.M.F. Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil). Mutat. Res., 2015, 771, 29-35.
[http://dx.doi.org/10.1016/j.mrfmmm.2014.11.004] [PMID: 25771977]
[7]
Matsuo, T.; Miyata, Y.; Asai, A.; Sagara, Y.; Furusato, B.; Fukuoka, J.; Sakai, H. Green Tea Polyphenol Induces Changes in Cancer-Related Factors in an Animal Model of Bladder Cancer. PLoS One, 2017, 12(1), e0171091.
[http://dx.doi.org/10.1371/journal.pone.0171091] [PMID: 28141864]
[8]
Kim, W.T.; Seo, S.P.; Byun, Y.J.; Kang, H.W.; Kim, Y.J.; Lee, S.C.; Jeong, P.; Song, H.J.; Choe, S.Y.; Kim, D.J.; Kim, S.K.; Ha, Y.S.; Moon, S.K.; Lee, G.T.; Kim, I.Y.; Yun, S.J.; Kim, W.J. The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M. Am. J. Chin. Med., 2018, 46(3), 689-705.
[http://dx.doi.org/10.1142/S0192415X18500362] [PMID: 29595070]
[9]
Davis-Searles, P.R.; Nakanishi, Y.; Kim, N.C.; Graf, T.N.; Oberlies, N.H.; Wani, M.C.; Wall, M.E.; Agarwal, R.; Kroll, D.J. Milk thistle and prostate cancer: Differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Res., 2005, 65(10), 4448-4457.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-4662] [PMID: 15899838]
[10]
Elyasi, S.; Hosseini, S.; Niazi Moghadam, M.R.; Aledavood, S.A.; Karimi, G. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother. Res., 2016, 30(11), 1879-1885.
[http://dx.doi.org/10.1002/ptr.5704] [PMID: 27555604]
[11]
Razavi, B.M.; Karimi, G. Protective effect of silymarin against chemical-induced cardiotoxicity. Iran. J. Basic Med. Sci., 2016, 19(9), 916-923.
[PMID: 27803777]
[12]
Ezzat, A.; Abdelhamid, A.O.; El Awady, M.K.; Abd El Azeem, A.S.; Mohammed, D.M. The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer. Biomed. Pharmacother., 2017, 95, 571-576.
[http://dx.doi.org/10.1016/j.biopha.2017.08.099] [PMID: 28869895]
[13]
Khorsandi, L.; Saki, G.; Bavarsad, N.; Mombeini, M. Silymarin induces a multi-targeted cell death process in the human colon cancer cell line HT-29. Biomed. Pharmacother., 2017, 94, 890-897.
[http://dx.doi.org/10.1016/j.biopha.2017.08.015] [PMID: 28810529]
[14]
Won, D.H.; Kim, L.H.; Jang, B.; Yang, I.H.; Kwon, H.J.; Jin, B.; Oh, S.H.; Kang, J.H.; Hong, S.D.; Shin, J.A.; Cho, S.D. In vitro and in vivo anti-cancer activity of silymarin on oral cancer. Tumour Biol., 2018, 40(5)
[http://dx.doi.org/10.1177/1010428318776170] [PMID: 29764340]
[15]
Wapenaar, H.; Dekker, F.J. Histone acetyltransferases: Challenges in targeting bi-substrate enzymes. Clin. Epigenetics, 2016, 8(1), 59.
[http://dx.doi.org/10.1186/s13148-016-0225-2] [PMID: 27231488]
[16]
Tyagi, A.; Raina, K.; Singh, R.P.; Gu, M.; Agarwal, C.; Harrison, G.; Glode, L.M.; Agarwal, R. Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine–induced urinary bladder carcinogenesis in male ICR mice. Mol. Cancer Ther., 2007, 6(12), 3248-3255.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2006] [PMID: 18089718]
[17]
Zeng, J.; Sun, Y.; Wu, K.; Li, L.; Zhang, G.; Yang, Z.; Wang, Z.; Zhang, D.; Xue, Y.; Chen, Y.; Zhu, G.; Wang, X.; He, D. Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria. Mol. Cancer Ther., 2011, 10(1), 104-116.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0577] [PMID: 21220495]
[18]
Zhu, X.X.; Ding, Y.H.; Wu, Y.; Qian, L.Y.; Zou, H.; He, Q. Silibinin: A potential old drug for cancer therapy. Expert Rev. Clin. Pharmacol., 2016, 9(10), 1323-1330.
[http://dx.doi.org/10.1080/17512433.2016.1208563] [PMID: 27362364]
[19]
Yin, X.; Zhang, B.H.; Zheng, S.S.; Gao, D.M.; Qiu, S.J.; Wu, W.Z.; Ren, Z.G. Coexpression of gene Oct4 and Nanog initiates stem cell characteristics in hepatocellular carcinoma and promotes epithelial-mesenchymal transition through activation of Stat3/Snail signaling. J. Hematol. Oncol., 2015, 8(1), 23.
[http://dx.doi.org/10.1186/s13045-015-0119-3] [PMID: 25879771]
[20]
Kaur, R.P.; Vasudeva, K.; Kumar, R.; Munshi, A. Role of p53 Gene in Breast Cancer: Focus on Mutation Spectrum and Therapeutic Strategies. Curr. Pharm. Des., 2018, 24(30), 3566-3575.
[http://dx.doi.org/10.2174/1381612824666180926095709] [PMID: 30255744]
[21]
Hirsch, C.L.; Smith-Windsor, E.L.; Bonham, K. Src family kinase members have a common response to histone deacetylase inhibitors in human colon cancer cells. Int. J. Cancer, 2006, 118(3), 547-554.
[http://dx.doi.org/10.1002/ijc.21383] [PMID: 16094635]
[22]
Gray, S.; Pandha, H.S.; Michael, A.; Middleton, G.; Morgan, R. HOX genes in pancreatic development and cancer. JOP, 2011, 12(3), 216-219.
[PMID: 21546695]
[23]
Zhang, Z.; Zhang, G.; Kong, C. Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor induces mitotic catastrophe and apoptosis in human bladder cancer cells. J. Cell. Mol. Med., 2017, 21(4), 758-767.
[http://dx.doi.org/10.1111/jcmm.13018] [PMID: 27878946]
[24]
Song, Y.; Chen, Y.; Li, Y.; Lyu, X.; Cui, J.; Cheng, Y.; Zheng, T.; Zhao, L.; Zhao, G. Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling. BioMed Res. Int., 2019, 2019, 1-14.
[http://dx.doi.org/10.1155/2019/1321973] [PMID: 31119150]
[25]
Chambers, C.; Valentova, K. kren, V. “Non-Taxifolin” Derived Flavonolignans: Phytochemistry and Biology. Curr. Pharm. Des., 2015, 21(38), 5489-5500.
[http://dx.doi.org/10.2174/1381612821666151002112720] [PMID: 26429716]
[26]
Yurtcu, E.; Darcansoy Iseri, O.; Iffet Sahin, F. Effects of silymarin and silymarin-doxorubicin applications on telomerase activity of human hepatocellular carcinoma cell line HepG2. J. BUON, 2015, 20(2), 555-561.
[PMID: 26011349]
[27]
Abenavoli, L.; Capasso, R.; Milic, N.; Capasso, F. Milk thistle in liver diseases: Past, present, future. Phytother. Res., 2010, 24(10), 1423-1432.
[http://dx.doi.org/10.1002/ptr.3207] [PMID: 20564545]
[28]
Fehér, P.; Ujhelyi, Z.; Váradi, J.; Fenyvesi, F.; Róka, E.; Juhász, B.; Varga, B.; Bombicz, M.; Priksz, D.; Bácskay, I.; Vecsernyés, M. Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes. Molecules, 2016, 21(10), 1269.
[http://dx.doi.org/10.3390/molecules21101269] [PMID: 27669200]
[29]
Gazák, R.; Walterová, D.; Kren, V. Silybin and silymarin--new and emerging applications in medicine. Curr. Med. Chem., 2007, 14(3), 315-338.
[http://dx.doi.org/10.2174/092986707779941159] [PMID: 17305535]
[30]
Surai, P. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants, 2015, 4(1), 204-247.
[http://dx.doi.org/10.3390/antiox4010204] [PMID: 26785346]
[31]
Procházková, D.; Boušová, I.; Wilhelmová, N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia, 2011, 82(4), 513-523.
[http://dx.doi.org/10.1016/j.fitote.2011.01.018] [PMID: 21277359]
[32]
Trouillas, P.; Marsal, P.; Svobodová, A.; Vostálová, J.; Gažák, R.; Hrbáč, J.; Sedmera, P.; Křen, V.; Lazzaroni, R.; Duroux, J.L.; Walterová, D. Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: A joint experimental and theoretical study. J. Phys. Chem. A, 2008, 112(5), 1054-1063.
[http://dx.doi.org/10.1021/jp075814h] [PMID: 18193843]
[33]
Iskender, B.; Izgi, K.; Karaca, H.; Canatan, H. Myrtucommulone-A treatment decreases pluripotency- and multipotency-associated marker expression in bladder cancer cell line HTB-9. J. Nat. Med., 2015, 69(4), 543-554.
[http://dx.doi.org/10.1007/s11418-015-0923-7] [PMID: 26054707]
[34]
O’Connor, M.L.; Xiang, D.; Shigdar, S.; Macdonald, J.; Li, Y.; Wang, T.; Pu, C.; Wang, Z.; Qiao, L.; Duan, W. Cancer stem cells: A contentious hypothesis now moving forward. Cancer Lett., 2014, 344(2), 180-187.
[http://dx.doi.org/10.1016/j.canlet.2013.11.012] [PMID: 24333726]
[35]
Chen, C.Y.; Lee, D.S.; Yan, Y.T.; Shen, C.N.; Hwang, S.M.; Lee, S.T.; Hsieh, P.C.H. Bcl3 Bridges LIF-STAT3 to Oct4 Signaling in the Maintenance of Naïve Pluripotency. Stem Cells, 2015, 33(12), 3468-3480.
[http://dx.doi.org/10.1002/stem.2201] [PMID: 26303070]
[36]
Jeter, C.R.; Liu, B.; Liu, X.; Chen, X.; Liu, C.; Calhoun-Davis, T.; Repass, J.; Zaehres, H.; Shen, J.J.; Tang, D.G. NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene, 2011, 30(36), 3833-3845.
[http://dx.doi.org/10.1038/onc.2011.114] [PMID: 21499299]
[37]
Fan, S.; Yu, Y.; Qi, M.; Sun, Z.; Li, L.; Yao, G.; Tashiro, S.I.; Onodera, S.; Ikejima, T. P53-mediated GSH depletion enhanced the cytotoxicity of NO in silibinin-treated human cervical carcinoma HeLa cells. Free Radic. Res., 2012, 46(9), 1082-1092.
[http://dx.doi.org/10.3109/10715762.2012.688964] [PMID: 22607092]
[38]
da Silva, G.N.; de Camargo, E.A.; Salvadori, D.M.F. Toxicogenomic activity of gemcitabine in two TP53-mutated bladder cancer cell lines: Special focus on cell cycle-related genes. Mol. Biol. Rep., 2012, 39(12), 10373-10382.
[http://dx.doi.org/10.1007/s11033-012-1916-1] [PMID: 23053941]
[39]
Tyagi, A.; Agarwal, C.; Harrison, G.; Glode, L.M.; Agarwal, R. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis, 2004, 25(9), 1711-1720.
[http://dx.doi.org/10.1093/carcin/bgh180] [PMID: 15117815]
[40]
Deep, G.; Singh, R.P.; Agarwal, C.; Kroll, D.J.; Agarwal, R. Silymarin and silibinin cause G1 and G2–M cell cycle arrest via distinct circuitries in human prostate cancer PC3 cells: A comparison of flavanone silibinin with flavanolignan mixture silymarin. Oncogene, 2006, 25(7), 1053-1069.
[http://dx.doi.org/10.1038/sj.onc.1209146] [PMID: 16205633]

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