1st International Conference on Chemo and BioInformatics, ICCBIKG  2021, (288-291)

AUTHOR(S) / АУТОР(И): Dragana S. Šeklić, Milena M. Jovanović, Nevena N. Milivojević, Marko N. Živanović


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DOI: 10.46793/ICCBI21.288S


Suppression of cell movement is an imperative in the effectiveness of future generations of chemotherapeutics. Frizzled 7 receptor (FZD7), as the first protein of Wnt/β-catenin signaling cascade, plays a significant role in regulation of cell differentiation, proliferation, and cell migration. This study aimed to investigate the potential effects of platinum (IV) complex: [PtCl4 (dbu-S, S-eddp)] – C1, and its corresponding ligand – L1 on cell movement, as well as the FZD7 expression and localization after treatments on two human colorectal carcinoma cell lines (HCT-116, SW-480). A Wound healing assay was used to examine cell migration, while FZD7 protein expression was examined by immunofluorescence. Chemical compounds, especially L1, reduced cell motility of both tested cell lines. They showed a particularly good effect on HCT-116 cells, increasing protein expression of the antimigratory marker FZD7 whose localization was observed on the cell membrane of HCT-116 cells. Suppression of cell movement was significantly lower in SW-480 cells after treatments, when compared to HCT-116, with an obvious decrease of FZD7 receptor expression and its localization in the cytoplasm of these cells. Our results indicate that among the examined treatments, the ligand showed more significant results in the suppression of HCT-116 cell movement, most likely through the stimulation of differentiation, which is indicated by the promotion of FZD7 expression.


immunofluorescence, cell migration, Wnt signal pathway


  • Altobelli, F. D’Aloisio, P.M. Angeletti., Colorectal cancer screening in countries of European Council outside of the EU-28, World Journal of Gastroenterology, 22 (2016) 4946-4957.
  • Lange, P.J. Bednarski., Evaluation for synergistic effects by combinations of photodynamic therapy (PDT) with temoporfin (mTHPC) and Pt(II) complexes carboplatin, cisplatin or oxaliplatin in a set of five human cancer cell lines, International Journal of Molecular Sciences, 19 (2018) 3183.
  • Zhang, S. Zhang, J. Yin, R. Xu., MiR-566 mediates cell migration and invasion in colon cancer cells by direct targeting of PSKH1, Cancer Cell International, 19 (2019) 333.
  • M. Samaei, Y. Yazdani, R. Alizadeh-Navaei, H. Azadeh, T. Farazmandfar., Promoter methylation analysis of WNT/β-catenin pathway regulators and its association with expression of DNMT1 enzyme in colorectal cancer, Journal of Biomedical Science, 21 (2014) 73.
  • T. MacDonald, X. He., Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling, Cold Spring Harbor Perspectives in Biology, 4 (2012) 12.pii: a007880.
  • D. King, W. Zhang, M.J. Suto, Y. Li., Frizzled7 as an emerging target for cancer therapy, Journal of Cell Signaling, 24(4) (2012) 846-851.
  • Vincan, D.J. Flanagan, N. Pouliot, T. Brabletz, S. Spaderna., Variable FZD7 expression incolorectal cancers indicates regulation by the tumour microenvironment. Developmental Dynamics, 239(1) (2010) 311-317.
  • Ueno, M. Hiura, Y. Suehiro, S. Hazama, H. Hirata, M. Oka, K. Imai, R. Dahiya, Y. Hinoda., Frizzled-7 as a potential therapeutic target in colorectal cancer, Neoplasia, 10(7) (2008) 697-705.
  • Quante, J. Varga, T.C. Wang, F.R. Greten., The gastrointestinal tumor microenvironment, World Journal of Gastroenterology, 145(1) (2013) 63-78.
  • U. Rehman, I.A. Rather., Myricetin abrogates cisplatin-induced oxidative stress, inflammatory response, and goblet cell disintegration in colon of wistar rats, Plants (Basel), 9 (2019) 28.
  • LJ. Stojković, V.V. Jevtić, G.P. Radić, D.S. Đačić, M.G. Ćurčić, S.D. Marković, V.M. Đinović, V.P. Petrović, S.R. Trifunović., Stereospecific ligands and their complexes. Part XII. Synthesis, characterization and in vitro antiproliferative activity of platinum(IV) complexes with some O,O ‘- dialkyl esters of (S,S)-ethylenediamine-N,N ‘-di-2-propanoic acid against colon cancer (HCT-116) and breast cancer (MDA-MB-231) cell lines, Journal of Molecular Structure, 1062 (2014) 21-28.
  • Kosanić, D. Šeklić, M. Jovanović, N. Petrović, S. Marković., Hygrophorus eburneus, edible mushroom, a promising natural bioactive agent, EXCLI Journal, 19 (2020) 442-457.
  • S. Šeklić, M.S. Stanković, M.G. Milutinović, M.D. Topuzović, A.S. Štajn, S.D. Marković., Cytotoxic, antimigratory and pro/antioxidative activities of extracts from medicinal mushrooms on colon cancer cell lines, Archives of Biological Sciences, 68 (2016) 93-105.
  • A. Schneider, W.S. Rasband, K.W. Eliceiri., NIH Image to ImageJ: 25 years of image analysis, Nature Methods, 9 (2012) 671-675.
  • Valenta, G. Hausmann, K. Baslera., The many faces and functions of β-catenin. The EMBO Journal, 31(12) (2012) 2714-2736.
  • Islam, M.H. Haque, S. Yadav, M.N. Islam, V. Gopalan, N.T. Nguyen, A.K. Lam, M.J.A. Shiddiky., An electrochemical method for sensitive and rapid detection of FAM134B protein in colon cancer samples, Scientific Reports, 7 (2017) 133.
  • Ueno, E. Shinto, Y. Kajiwara, S. Fukazawa, H. Shimazaki, J. Yamamoto, K. Hase., Prognosticimpact of histological categorisation of epithelial-mesenchymal transition incolorectal cancer, British Journal of Cancer, 111 (2014) 2082-2090.