Effect of prevalent polychlorinated biphenyls (PCBs) food contaminant on the MCF7, LNCap and MDA-MB-231 cell lines viability and PON1 gene expression level: proposed model of binding

Abstract

Background

Polychlorinated biphenyls (PCBs) are a group of synthetic organic chlorine compounds known as an organic pollutant in food sources, which play important roles in malignancies. The present study aimed to investigate the direct effects of prevalent PCBs in food in hormone-responsive and non-responsive cell lines.

Methods

In the current study, MCF-7, LNCap, and MDA-MB231 cell lines were treated with serial concentrations (0.001–100 μM) of PCBs for 48 h and cell viability assessment was performed using MTT assay. The best concentration then applied and the expression level of PON1 was evaluated using real-time PCR. Besides, molecular docking was performed to determine the binding mechanism and predicted binding energies of PBCs compounds to the AhR receptor.

Results

Unlike MCF-7 and LNCap cells, the viability of MDA-MB231 cells did not significantly change by different concentrations of PCBs. Meanwhile, quantitative gene expression analysis showed that the PON1 was significantly more expressed in MCF-7 and LNCap lines treated with PCB28 and PCB101. However, the expression level of this gene in other groups and also MDA-MB231cells did not demonstrate any significantly change. Also, the results of molecular docking showed that PBCs had steric interaction with AhR receptor.

Conclusions

Current results showed that despite of hormone non-responsive cells the PCBs have a significant positive effect on hormone-responsive cell. Therefore, and regarding to the existence of PCBs contamination in food there should be serious concern about their impact on the prevalence of different malignancies which certainly should result in a standard limit for this material.

Graphical abstract

This study aimed to investigate the direct effects of prevalent PCBs in food in hormone-responsive and non-responsive cell lines. Cell lines were treated with serial concentrations of PCBs and cell viability assessment was performed using MTT assay. The expression level of PON1 was evaluated using real-time PCR. Molecular docking was performed to determine the binding mechanism and predicted binding energies of PBCs compounds to the AhR receptor. PCBs contamination in food there should be serious concern about their impact on the prevalence of different malignancies which certainly should result in a standard limit for this material.

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References

  1. 1.

    Wen Y, Schoups G, van de Giesen N. Organic pollution of rivers: combined threats of urbanization, livestock farming and global climate change. Sci Rep. 2017;7(1):1–9. https://doi.org/10.1038/srep43289.

  2. 2.

    Dhakal K, Gadupudi GS, Lehmler HJ, Ludewig G, Duffel MW, Robertson LW. Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs). Environ Sci Pollut Res Int. 2018;25:16277–90. https://doi.org/10.1007/s11356-017-9694-x.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Crinnion WJ. Polychlorinated biphenyls: persistent pollutants with immunological, neurological, and endocrinological consequences. Altern Med Rev. 2011;16(1):5–13.

    PubMed  Google Scholar 

  4. 4.

    Jayaraj R, Megha P, Sreedev P. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment. Interdiscip Toxicol. 2016;9:90–100. https://doi.org/10.1515/intox-2016-0012.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Roszko M, Jedrzejczak R, Szymczyk K. Polychlorinated biphenyls (PCBs), polychlorinated diphenyl ethers (PBDEs) and organochlorine pesticides in selected cereals available on the polish retail market. Sci Total Environ. 2014;466-467:136–51. https://doi.org/10.1016/j.scitotenv.2013.07.016.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Chovancova J, Conka K, Kocan A, Sejakova ZS. PCDD, PCDF, PCB and PBDE concentrations in breast milk of mothers residing in selected areas of Slovakia. Chemosphere. 2011;83:1383–90. https://doi.org/10.1016/j.chemosphere.2011.02.070.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Koh WX, Hornbuckle KC, Wang K, Thorne PS. Serum polychlorinated biphenyls and their hydroxylated metabolites are associated with demographic and behavioral factors in children and mothers. Environ Int. 2016;94:538–45. https://doi.org/10.1016/j.envint.2016.06.014.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Brazova T, Hanzelova V, Miklisova D. Bioaccumulation of six PCB indicator congeners in a heavily polluted water reservoir in eastern Slovakia: tissue-specific distribution in fish and their parasites. J Parasitol Res. 2012;111:779–86. https://doi.org/10.1007/s00436-012-2900-3.

    Article  Google Scholar 

  9. 9.

    European Food Safety Authority (EFSA). Opinion of the scientific panel on contaminants in the food chain on a request from the commission related to the presence of non-dioxin like polychlorinated biphenyls (PCB) in feed and food. EFSA J. 2005;3:1–137.

    Google Scholar 

  10. 10.

    Vondracek J, Machala M, Bryja V, Chramostova K, Krcmar P, Dietrich C, et al. Aryl hydrocarbon receptor-activating polychlorinated biphenyls and their hydroxylated metabolites induce cell proliferation in contact-inhibited rat liver epithelial cells. Toxicol Sci. 2005;83:53–63. https://doi.org/10.1093/toxsci/kfi009.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;2005:293–342. https://doi.org/10.1210/er.2009-0002.

    CAS  Article  Google Scholar 

  12. 12.

    Kolluri SK, Jin UH, Safe S. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target. Arch Toxicol. 2017;91:2497–513. https://doi.org/10.1007/s00204-017-1981-2.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Dietrich C. Antioxidant functions of the aryl hydrocarbon receptor. Stem Cells Int. 2016;2016:1–10. https://doi.org/10.1155/2016/7943495.

    CAS  Article  Google Scholar 

  14. 14.

    Vázquez SM, Mladovan A, Garbovesky C, Baldi A, Lüthy IA. Three novel hormone-responsive cell lines derived from primary human breast carcinomas: functional characterization. J Cell Physiol. 2004;199:460–9. https://doi.org/10.1002/jcp.10466.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Turgut Cosan D, Colak E, Saydam F, Yazıcı H, Degirmenci I, Birdane A, et al. Association of paraoxonase 1 (PON1) gene polymorphisms and concentration with essential hypertension. Clin Exp Hypertens. 2016;38:602–7. https://doi.org/10.3109/10641963.2016.1174255.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Sakurai S, Shimizu T, Ohto UJJo BC. The crystal structure of the AhRR–ARNT heterodimer reveals the structural basis of the repression of AhR-mediated transcription. J Biol Chem. 2017;292:17609–16. https://doi.org/10.1074/jbc.M117.812974.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Naeem S, Hylands P, Barlow D. Docking studies of chlorogenic acid against aldose redutcase by using molgro virtual docker software. J Appl Pharm Sci. 2013;3(1):13. https://doi.org/10.7324/JAPS.2013.30104.

  18. 18.

    Ptak A, Mazur K, Gregoraszczuk EL. Comparison of combinatory effects of PCBs (118, 138, 153 and 180) with 17 beta-estradiol on proliferation and apoptosis in MCF-7 breast cancer cells. Toxicol Ind Health. 2011;27:315–21. https://doi.org/10.1177/0748233710387003.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Endo F, Monsees TK, Akaza H, Schill W-B, Pflieger-Bruss S. Effects of single non-ortho, mono-ortho, and di-ortho chlorinated biphenyls on cell functions and proliferation of the human prostatic carcinoma cell line, LNCaP. Reprod Toxicol. 2003;17:229–36. https://doi.org/10.1016/s0890-6238(02)00126-0.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Radice S, Chiesara E, Fucile S, Marabini L. Different effects of PCB101, PCB118, PCB138 and PCB153 alone or mixed in MCF-7 breast cancer cells. Food Chem Toxicol. 2008;46:2561–7. https://doi.org/10.1016/j.fct.2008.04.012.

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Robertson LW, Ludewig G. Polychlorinated biphenyl (PCB) carcinogenicity with special emphasis on airborne PCBs. Gefahrst Reinhalt Luft. 2011;71(1–2):25–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Milon A, Opydo-Chanek M, Tworzydlo W, Galas J, Pardyak L, Kaminska A, et al. Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells. Cell Tissue Res. 2017;369:429–44. https://doi.org/10.1007/s00441-017-2596-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Dutta SK, Mitra PS, Ghosh S, Zang S, Sonneborn D, Hertz-Picciotto I, et al. Differential gene expression and a functional analysis of PCB-exposed children: understanding disease and disorder development. Environ Int. 2012;40:143–54. https://doi.org/10.1016/j.envint.2011.07.008.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Burow ME, Tang Y, Collins-Burow BM, Krajewski S, Reed JC, JA ML, et al. Effects of environmental estrogens on tumor necrosis factor α-mediated apoptosis in MCF-7 cells. Carcinogenesis. 1999;20(11):2057–2061. https://doi.org/10.1093/carcin/20.11.2057.

  25. 25.

    Spink BC, Pang S, Pentecost BT, Spink DC. Induction of cytochrome P450 1B1 in MDA-MB-231 human breast cancer cells by non-ortho-substituted polychlorinated biphenyls. Toxicol in Vitro. 2002;16:695–704. https://doi.org/10.1016/s0887-2333(02)00091-7.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Liu S, Li S, Du Y. Polychlorinated biphenyls (PCBs) enhance metastatic properties of breast Cancer cells by activating rho-associated kinase (ROCK). PLoS One. 2010;5:e11272. https://doi.org/10.1371/journal.pone.0011272.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Leijs MM, Gan L, De Boever P, Esser A, Amann PM, Ziegler P, et al. Altered gene expression in dioxin-like and non-dioxin-like PCB exposed peripheral blood mononuclear cells. Int J Environ Res Public Health. 2019;16(12):2090. https://doi.org/10.3390/ijerph16122090.

  28. 28.

    Champion S, Sauzet C, Bremond P, Benbrahim K, Abraldes J, Seree E, et al. Activation of the NF kappa B pathway enhances AhR expression in intestinal Caco-2 cells. ISRN Toxicol. 2013;2013:1–7. https://doi.org/10.1155/2013/792452.

    CAS  Article  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Mahdi Taherian and Dr. Hassan Noor-Bazargan for their constructive comments on our manuscript.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Fatemeh Yazdi], [Akram Eidi] and [Shahram Shoeibi]. The first draft of the manuscript was written by [Fatemeh Yazdi] and revised by [Mohammad Hossein Yazdi] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mohammad Hossein Yazdi.

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Yazdi, F., Shoeibi, S., Yazdi, M.H. et al. Effect of prevalent polychlorinated biphenyls (PCBs) food contaminant on the MCF7, LNCap and MDA-MB-231 cell lines viability and PON1 gene expression level: proposed model of binding. DARU J Pharm Sci (2021). https://doi.org/10.1007/s40199-021-00394-9

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Keywords

  • Aryl hydrocarbon receptor
  • Cell viability
  • Food contamination
  • Molecular docking
  • PON1