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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

A Ferrocene Derivative Reduces Cisplatin Resistance in Breast Cancer Cells through Suppression of MDR-1 Expression and Modulation of JAK2/STAT3 Signaling Pathway

Author(s): Shokoofe Noori, Mitra Nourbakhsh, Shabnam Farzaneh and Afshin Zarghi*

Volume 20, Issue 18, 2020

Page: [2285 - 2292] Pages: 8

DOI: 10.2174/1871520620666200807103903

Price: $65

Abstract

Background: Breast cancer is the most common kind of cancer among women in the world. Despite major cancer therapy successes in recent years, cancer cells usually develop mechanisms to survive chemotherapy- induced cell death. Therefore, new strategies are needed to reverse cancer chemoresistance.

Objective: The aim of this study was to investigate the effect of a recently-synthesized ferrocene derivative named 1-ferrocenyl-3-(4-methylsulfonylphenyl)propen-1-one (FMSP) on cisplatin resistance in MCF-7 cells, focusing on its inhibitory effects on Multi-Drug Resistance-1 (MDR-1) and inflammatory-related STAT3 pathway.

Methods: Cisplatin-resistant MCF-7 cells were developed and the effect of cisplatin and FMSP on cell viability was examined by MTT assay. RT-PCR and Western blotting analyses were performed to assess the gene and protein expression of MDR-1 as well as phosphorylation of JAK2 and STAT3.

Results: Overexpression of MDR1 as well as a marked increase in the level of phosphorylated STAT3 was observed in cisplatin-resistant MCF-7 (MCF-7R) cells. FMSP successfully reduced the MCF-7R cell viability and reversed both MDR1 expression and STAT3 phosphorylation status through which sensitivity of MCF-7R cells to cisplatin treatment was regained.

Conclusion: Our results indicated that FMSP may be considered as a promising therapeutic agent for the prevention and management of chemoresistance in breast cancer cells.

Keywords: Breast cancer, ferrocene, cisplatin, JAK2, STAT3, MDR-1, chemoresistance.

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[1]
Redig, A.J.; McAllister, S.S. Breast cancer as a systemic disease: A view of metastasis. J. Intern. Med., 2013, 274(2), 113-126.
[http://dx.doi.org/10.1111/joim.12084] [PMID: 23844915]
[2]
Feng, Y.; Spezia, M.; Huang, S.; Yuan, C.; Zeng, Z.; Zhang, L.; Ji, X.; Liu, W.; Huang, B.; Luo, W.; Liu, B.; Lei, Y.; Du, S.; Vuppalapati, A.; Luu, H.H.; Haydon, R.C.; He, T-C.; Ren, G. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis., 2018, 5(2), 77-106.
[http://dx.doi.org/10.1016/j.gendis.2018.05.001] [PMID: 30258937]
[3]
Jatoi, I.; Benson, J.R.; Kunkler, I. Hypothesis: Can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? NPJ Breast Cancer, 2018, 4(1), 8.
[http://dx.doi.org/10.1038/s41523-018-0061-y] [PMID: 29644338]
[4]
Gomes, L.R.; Rocha, C.R.R.; Martins, D.J.; Fiore, A.P.Z.P.; Kinker, G.S.; Bruni-Cardoso, A.; Menck, C.F.M. ATR mediates cisplatin resistance in 3D-cultured breast cancer cells via translesion DNA synthesis modulation. Cell Death Dis., 2019, 10(6), 459.
[http://dx.doi.org/10.1038/s41419-019-1689-8] [PMID: 31189884]
[5]
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]
[6]
Basu, A.; Krishnamurthy, S. Cellular responses to Cisplatin-induced DNA damage. J. Nucleic Acids, 2010, 2010201367
[http://dx.doi.org/10.4061/2010/201367] [PMID: 20811617]
[7]
Leon-Galicia, I.; Diaz-Chavez, J.; Albino-Sanchez, M.E.; Garcia-Villa, E.; Bermudez-Cruz, R.; Garcia-Mena, J.; Herrera, L.A.; García-Carrancá, A.; Gariglio, P. Resveratrol decreases Rad51 expression and sensitizes cisplatin resistant MCF 7 breast cancer cells. Oncol. Rep., 2018, 39(6), 3025-3033.
[http://dx.doi.org/10.3892/or.2018.6336] [PMID: 29620223]
[8]
Jaouen, G.; Vessières, A.; Top, S. Ferrocifen type anti cancer drugs. Chem. Soc. Rev., 2015, 44(24), 8802-8817.
[http://dx.doi.org/10.1039/C5CS00486A] [PMID: 26486993]
[9]
Pérez, W.I.; Soto, Y.; Ortíz, C.; Matta, J.; Meléndez, E. Ferrocenes as potential chemotherapeutic drugs: Synthesis, cytotoxic activity, reactive oxygen species production and micronucleus assay. Bioorg. Med. Chem., 2015, 23(3), 471-479.
[http://dx.doi.org/10.1016/j.bmc.2014.12.023] [PMID: 25555734]
[10]
Patra, M.; Gasser, G. The medicinal chemistry of ferrocene and its derivatives. Nat. Rev. Chem, 2017, 1(9) 0066
[http://dx.doi.org/10.1038/s41570-017-0066]
[11]
Farzaneh, S.; Zeinalzadeh, E.; Daraei, B.; Shahhosseini, S.; Zarghi, A. New ferrocene compounds as selective Cyclooxygenase (COX-2) inhibitors: Design, synthesis, cytotoxicity and enzyme-inhibitory activity. Anticancer. Agents Med. Chem., 2018, 18(2), 295-301.
[http://dx.doi.org/10.2174/1871520617666171003145533] [PMID: 28971779]
[12]
Nourbakhsh, M.; Farzaneh, S.; Taghikhani, A.; Zarghi, A.; Noori, S. The effect of a newly synthesized ferrocene derivative against MCF-7 breast cancer cells and spheroid stem cells through ROS production and inhibition of JAK2/STAT3 signaling pathway. Anticancer. Agents Med. Chem., 2020, 20(7), 875-886.
[http://dx.doi.org/10.2174/1871520620666200101151743] [PMID: 31893999]
[13]
Lohitesh, K.; Chowdhury, R.; Mukherjee, S. Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: An insight. Cancer Cell Int., 2018, 18, 44-44.
[http://dx.doi.org/10.1186/s12935-018-0538-7] [PMID: 29568237]
[14]
Katayama, K.; Noguchi, K.; Sugimoto, Y. Regulations of P-glycoprotein/ABCB1/MDR1 in human cancer cells. New J. Sci., 2014, 2014, 10.
[http://dx.doi.org/10.1155/2014/476974]
[15]
Wang, Z.; Wang, C.; Zuo, D.; Zhang, T.; Yin, F.; Zhou, Z.; Wang, H.; Xu, J.; Mao, M.; Wang, G.; Hua, Y.; Sun, W.; Cai, Z. Attenuation of STAT3 phosphorylation promotes apoptosis and chemosensitivity in human osteosarcoma induced by Raddeanin A. Int. J. Biol. Sci., 2019, 15(3), 668-679.
[http://dx.doi.org/10.7150/ijbs.30168] [PMID: 30745853]
[16]
Zhang, X.; Xiao, W.; Wang, L.; Tian, Z.; Zhang, J. Deactivation of signal transducer and activator of transcription 3 reverses chemotherapeutics resistance of leukemia cells via down-regulating P-gp. PLoS One, 2011, 6(6)e20965
[http://dx.doi.org/10.1371/journal.pone.0020965] [PMID: 21677772]
[17]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 2001, 25(4), 402-408.
[18]
Masjedi, A.; Hashemi, V.; Hojjat-Farsangi, M.; Ghalamfarsa, G.; Azizi, G.; Yousefi, M.; Jadidi-Niaragh, F. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomed. Pharmacother., 2018, 108, 1415-1424.
[http://dx.doi.org/10.1016/j.biopha.2018.09.177] [PMID: 30372844]
[19]
Sansone, P.; Bromberg, J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J. Clin. Oncol., 2012, 30(9), 1005-1014.
[http://dx.doi.org/10.1200/JCO.2010.31.8907] [PMID: 22355058]
[20]
Becker, S.; Groner, B.; Müller, C.W. Three-dimensional structure of the Stat3beta homodimer bound to DNA. Nature, 1998, 394(6689), 145-151.
[http://dx.doi.org/10.1038/28101] [PMID: 9671298]
[21]
Wang, X.; Zhang, H.; Chen, X. Drug resistance and combating drug resistance in cancer. Canc. Drug Resist., 2019, 2, 141-160.
[http://dx.doi.org/10.20517/cdr.2019.10]
[22]
Casals, E.; Gusta, M.F.; Cobaleda-Siles, M.; Garcia-Sanz, A.; Puntes, V.F. Cancer resistance to treatment and antiresistance tools offered by multimodal multifunctional nanoparticles. Cancer Nanotechnol., 2017, 8(1), 7.
[http://dx.doi.org/10.1186/s12645-017-0030-4] [PMID: 29104700]
[23]
Alimbetov, D.; Askarova, S.; Umbayev, B.; Davis, T.; Kipling, D. Pharmacological targeting of cell cycle, apoptotic and cell adhesion signaling pathways implicated in chemoresistance of cancer cells. Int. J. Mol. Sci., 2018, 19(6), 1690.
[http://dx.doi.org/10.3390/ijms19061690] [PMID: 29882812]
[24]
Pérès, B.; Nasr, R.; Zarioh, M.; Lecerf-Schmidt, F.; Di Pietro, A.; Baubichon-Cortay, H.; Boumendjel, A. Ferrocene-embedded flavonoids targeting the Achilles heel of multidrug-resistant cancer cells through collateral sensitivity. Eur. J. Med. Chem., 2017, 130, 346-353.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.064] [PMID: 28273561]
[25]
Podolski-Renić, A.; Bősze, S.; Dinić, J.; Kocsis, L.; Hudecz, F.; Csámpai, A.; Pešić, M. Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel. Metallomics, 2017, 9(8), 1132-1141.
[http://dx.doi.org/10.1039/C7MT00183E] [PMID: 28737782]
[26]
Reiter, C.; Capcı Karagöz, A.; Fröhlich, T.; Klein, V.; Zeino, M.; Viertel, K.; Held, J.; Mordmüller, B.; Emirdağ Öztürk, S.; Anıl, H.; Efferth, T.; Tsogoeva, S.B. Synthesis and study of cytotoxic activity of 1,2,4-trioxane- and egonol-derived hybrid molecules against Plasmodium falciparum and multidrug-resistant human leukemia cells. Eur. J. Med. Chem., 2014, 75, 403-412.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.043] [PMID: 24561670]
[27]
Spoerlein-Guettler, C.; Mahal, K.; Schobert, R.; Biersack, B. Ferrocene and (arene)ruthenium(II) complexes of the natural anticancer naphthoquinone plumbagin with enhanced efficacy against resistant cancer cells and a genuine mode of action. J. Inorg. Biochem., 2014, 138, 64-72.
[http://dx.doi.org/10.1016/j.jinorgbio.2014.04.020] [PMID: 24907976]
[28]
Zheng, H-C. The molecular mechanisms of chemoresistance in cancers. Oncotarget, 2017, 8(35), 59950-59964.
[http://dx.doi.org/10.18632/oncotarget.19048] [PMID: 28938696]
[29]
Zhang, X.; Ren, D.; Wu, X.; Lin, X.; Ye, L.; Lin, C.; Wu, S.; Zhu, J.; Peng, X.; Song, L. miR-1266 contributes to pancreatic cancer progression and chemoresistance by the STAT3 and NF-κB signaling pathways. Mol. Ther. Nucleic Acids, 2018, 11, 142-158.
[http://dx.doi.org/10.1016/j.omtn.2018.01.004] [PMID: 29858050]
[30]
Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull., 2017, 7(3), 339-348.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[31]
Zhao, C.; Li, H.; Lin, H-J.; Yang, S.; Lin, J.; Liang, G. Feedback activation of STAT3 as a cancer drug-resistance mechanism. Trends Pharmacol. Sci., 2016, 37(1), 47-61.
[http://dx.doi.org/10.1016/j.tips.2015.10.001] [PMID: 26576830]
[32]
Lee, H.; Jeong, A.J.; Ye, S-K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep., 2019, 52(7), 415-423.
[http://dx.doi.org/10.5483/BMBRep.2019.52.7.152] [PMID: 31186087]
[33]
Wieczorek, A.; Błauż, A.; Zakrzewski, J.; Rychlik, B.; Plażuk, D. Ferrocenyl 2,5-piperazinediones as tubulin-binding organometallic ABCB1 and ABCG2 inhibitors active against MDR cells. ACS Med. Chem. Lett., 2016, 7(6), 612-617.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00046] [PMID: 27326336]
[34]
Bárány, P.; Oláh, R.S.; Kovács, I.; Czuczi, T.; Szabó, C.L.; Takács, A.; Lajkó, E.; Láng, O.; Kőhidai, L.; Schlosser, G.; Bősze, S.; Mező, G.; Hudecz, F.; Csámpai, A. Ferrocene-containing impiridone (ONC201) hybrids: Synthesis, DFT modelling, in vitro evaluation, and structure−activity relationships. Molecules, 2018, 23(9), 2248.
[http://dx.doi.org/10.3390/molecules23092248] [PMID: 30177664]

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