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  • 1 Faculty of Medicine, Maltepe University, Turkey
  • 2 Maltepe University, Turkey
  • 3 Faculty of Medicine, Maltepe University, Turkey
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Introduction

Hepatocellular carcinoma (HCC) is found within the first five most common tumors worldwide. Sorafenib is an approved agent in HCC treatment. Sertraline is a selective serotonin reuptake inhibitor. The aim of the study is to investigate the combination of sertraline and sorafenib at hepatocellular cancer cell proliferation and death.

Methods

HepG2 cells were treated with drugs and viability test XTT was performed. Cells were stained with hematoxylin and eosin for histological examination or with anti-Bcl-2 antibody and Hoechst 33258 for immunofluorescence.

Results

Viability results supported dose-dependent antiproliferative effect for both sertraline and sorafenib. Microscopic evaluation of stained cells exerts morphological changes.

Discussion

This is the first study to show that sorafenib and sertraline have synergistic effect in hepatocellular cancer.

  • Ashburn, T. T., Thor, K. B. (2004) Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov. 3, 673683.

  • Bellmunt, J., Eisen, T., Fishman, M., Quinn, D. (2011) Experience with sorafenib and adverse event management. Crit. Rev. Oncol. Hematol. 78, 2432.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Bliss, C. I. (1939) The toxicity of poisons applied jointly. Ann. Appl. Biol. 26, 585615.

  • Cervello, M., Bachvarov, D., Lampiasi, N., Cusimano, A., Azzolina, A., McCubrey, J.A., Montalto, G. (2012) Molecular mechanisms of sorafenib action in liver cancer cells. Cell Cycle 11, 28432855.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Chan, H. L., Chi, W. C., Chen, V. C., Huang, K. Y., Wang, T. N., Lee, Y., McIntyre, R. S., Hsu, T. C., Lee, C. T., Tzang, B. S. (2018) SSRIs associated with decreased risk of hepatocellular carcinoma: a population-based case-control study. Psychooncology 27, 187192.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Chang, C. H., Chen, S. J., Liu, C. Y. (2015) Risk of developing depressive disorders following hepatocellular carcinoma: a nationwide population-based study. PLoS One 10, e0135417.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Chen, S., Xuan, J., Couch, L., Iyer, A., Wu, Y., Li, Q. Z., Guo, L. (2014a) Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology 322, 7888.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Chen, S., Xuan, J., Wan, L., Lin, H., Couch, L., Mei, N., Dobrovolsky, V. N., Guo, L. (2014b) Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol. Sci. 137, 404415.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Daher, S., Massarwa, M., Benson, A. A., Khoury, T. (2017) Current and future treatment of hepatocellular carcinoma: an updated comprehensive review. J Clin. Transl. Hepatol. 6, 6978.

    • Search Google Scholar
    • Export Citation
  • DeVane, C. L., Liston, H. L., Markowitz, J. S. (2002) Clinical pharmacokinetics of sertraline. Clin. Pharmacokinet. 41, 12471266.

  • Fishback, J. A., Robson, M. J., Xu, Y. T., Matsumoto, R. R. (2010) Sigma receptors: potential targets for a new class of antidepressant drug. Pharmacol. Ther. 127, 271282.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ghouri, Y. A., Mian, I., Rowe, J. H. (2017) Review of hepatocellular carcinoma: epidemiology, etiology, and carcinogenesis. J. Carcinog. 16, 1.

  • Gil-Ad, I., Zolokov, A., Lomnitski, L., Taler, M., Bar, M., Luria, D., Ram, E., Weizman, A. (2008) Evaluation of the potential anti-cancer activity of the antidepressant sertraline in human colon cancer cell lines and in colorectal cancer-xenografted mice. Int. J Oncol. 33, 277286.

    • Search Google Scholar
    • Export Citation
  • Hoetelmans, R., Van Slooten, H. J., Keijzer, R., Erkeland, S., van de Velde, C. J., Dierendonck, J. H. (2000) Bcl-2 and Bax proteins are present in interphase nuclei of mammalian cells. Cell Death Differ. 7, 384392.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ianevski, A., He, L., Aittokallio, T., Tang, J. (2017) SynergyFinder: a web application for analyzing drug combination dose–response matrix data. Bioinformatics 33, 24132415.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Huang, J., Zhao, D., Liu, Z., Liu, F. (2018) Repurposing psychiatric drugs as anti-cancer agents. Cancer Lett. 419, 257265.

  • Joong, S. S., Liu, J. O. (2014) Recent advances in drug repositioning for the discovery of new anticancer drugs. Int. J. Biol. Sci. 10, 654663.

  • Keating, G. M., Santoro, A. (2009) Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs 69, 223240.

  • Kuwahara, J., Takaaki, Y., Nobuaki, E., Mitsuyo, U., Nina, Z., Soichiro, U., Satohiro, M. (2015) Comparison of the anti-tumor effects of selective serotonin reuptake inhibitors as well as serotonin and norepinephrine reuptake inhibitors in human hepatocellular carcinoma cells. Biol. Pharm. Bull. 38, 14101414.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Liang, C., Chen, W., Zhi, X., Ma, T., Xia, X., Liu, H., Zhang, Q., Hu, Q., Hang, Y., Bai, X., Liang, T. (2013) Serotonin promotes the proliferation of serum-deprived hepatocellular carcinoma cells via upregulation of FOXO3a. Mol. Cancer 12, 14.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ozunal, Z. G. (2014) Drug development, drug repositioning in oncology. In: 19th World Congress on Advances in Oncology and 17th International Symposium on Molecular Medicine, Athens, Greece, October 9–11, 2014.

    • Export Citation
  • Patt, Y., Rojas-Hernandez, C., Fekrazad, H. M., Bansal, P., Lee, F. C. (2017) Phase II trial of sorafenib in combination with capecitabine in patients with hepatocellular carcinoma: INST 08-20. Oncologist 22, 11581160.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Peng, L., Gu, L., Li, B., Hertz, L. (2014) Fluoxetine and all other SSRIs are 5-HT2B Agonists – importance for their therapeutic effects. Cur. Neuropharmacol. 12, 365379.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Raza, A., Sood, G. K. (2014) Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J. Gastroenterol. 20, 41154127.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Reddy, K. K., Lefkove, B., Chen, L. B., Govindarajan, B., Carracedo, A., Velasco, G., Carrillo, C. O., Bhandarkar, S. S., Owens, M. J., Mechta-Grigoriou, F., Arbiser, J. L. (2008) The antidepressant sertraline downregulates Akt and has activity against melanoma cells. Pigment Cell Melanoma Res. 21, 451456.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Sarrouilhe, D., Clarhaut, J., Defamie, N., Mesnil, M. (2015) Serotonin and cancer: what is the link? Curr. Mol. Med. 15, 6277.

  • Schrödter, S., Braun, M., Syring, I., Klümper, N., Deng, M., Schmidt, D., Perner, S., Mülle, R. S. C., Ellinger, J. (2016) Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma. Mol. Cancer 15, 10.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Soll, C., Riener, M. O., Oberkofler, C. E., Hellerbrand, C., Wild, P. J., DeOliveira, M. L., Clavien, P. A. (2012) Expression of serotonin receptors in human hepatocellular cancer. Clin. Cancer Res. 18, 59025910.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Tesei, A., Cortesi, M., Zamagni, A., Arienti, C., Pignatta, S., Zanoni, M., Paolillo, M., Curti, D., Rui, M., Rossi, D., Collina, S. (2018) Sigma receptors as endoplasmic reticulum stress “Gatekeepers” and their modulators as emerging new weapons in the fight against cancer. Front. Pharmacol. 9, 711.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Wei, J. C., Meng, F. D., Qu, K., Wang, Z. X., Wu, Q. F., Zhang, L. Q., Pang, Q., Liu, C. (2015) Sorafenib inhibits proliferation and invasion of human hepatocellular carcinoma cells via up-regulation of p53 and suppressing FoxM1. Acta Pharmacol. Sin. 36, 241251.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Xia, D., Zhang, Y. T., Xu, G. P., Yan, W. W., Pan, X. R., Tong, J. H. (2017) Sertraline exerts its antitumor functions through both apoptosis and autophagy pathways in acute myeloid leukemia cells. Leukemia & Lymphoma 58, 22082217.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Xu, J. J., Wang, S. Y., Chen, Y., Chen, G. P., Li, Z. Q., Shao, X. Y., Li, L., Lu, W., Zhou, T. Y. (2014) Dopamine D1 receptor activation induces dehydroepiandrosterone sulfotransferase (SULT2A1) in HepG2 cells. Acta Pharmacol. Sin. 35, 889898.

    • Crossref
    • Search Google Scholar
    • Export Citation

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Senior Editors

Editor-in-Chief: Miklósi, Ádám

Managing Editor: Molnár, Csaba

Editorial Board

Maász, Gábor - Hungarian Academy of Sciences, Centre for Ecological Research
Barina, Zoltán - Hungarian Natural History Museum, Department of Botany
Pongrácz, Péter - Eötvös Loránd University, Department of Ethology
Gábriel, Róbert - University of Pécs, Szentágothai Research Centre
Vágvölgyi, Csaba - University of Szeged, Department of Microbiology
Hideg, Éva - University of Pécs, Department of Plant Biology
Solti, Ádám - Eötvös Loránd University, Department of Plan Physiology and Molecular Plant Biology
Erős, Tibor - Hungarian Academy of Sciences, Centre for Ecological Research
Székely, Tamás - University of Bath, University of Debrecen
Dobolyi, Árpád - Eötvös Loránd University, Department of Neurobiology and Physiology
Tamás, Andrea - University of Pécs, Department of Anatomy
Kovács, Tibor - Eötvös Loránd University, Department of Genetics
Serfőző, Zoltán - Hungarian Academy of Sciences, Balaton Limnological Institute
Bede-Fazekas, Ákos - Hungarian Academy of Sciences, Centre for Ecological Research
Bugyi, Beáta - University of Pécs, Department of Biophysics
Fugazza, Claudia - Eötvös Loránd University, Department of Ethology
Chmura, Damjan - University of Bielsko-Biala, Institute of Environmental Protection and Engineering
Neugart, Susanne - Leibniz Institute of Vegetable and Ornamental Crops
Contardo-Jara, Valeska - Technical University of Berlin, Institute of Ecology