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In Vitro Cytotoxicity Study of Cyclophosphamide, Etoposide and Paclitaxel on Monocyte Macrophage Cell Line Raw 264.7

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Abstract

The presence of antineoplastic compounds in aquatic ecosystem is an emerging challenge for the society. Antineoplastic compounds released into the aquatic environment exhibit a potential threat to normal aquatic life. Particularly, antineoplastic compounds are responsible for direct or indirect interference with the cellular DNA of an organism and cause toxicity to cells. The present study focused on the assessment of in vitro toxic effect of cyclophosphamide, etoposide and paclitaxel on Raw 264.7 cell line (mouse monocyte macrophage cells). The inhibitory concentration of cyclophosphamide, etoposide, and paclitaxel was determined. The IC50 values of these compounds were 145.44, 5.40, and 69.76 µg ml−1 respectively. This is the first report on toxicity analysis of cyclophosphamide, paclitaxel and etoposide on Raw 264.7 cell line by reducing cell viability and indicating the cell cytotoxicity i.e., 69.58% for cyclophosphamide, 92.01% for etoposide and 88.85% for paclitaxel on concentration 250 µg ml−1. The results of their cytotoxicity assessment highlight the need of improvement in sewage treatment technology for the efficient removal of these compounds from aquatic environment.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  2. Besse JP, Latour JF, Garric J (2012) Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs? Environ Int 39:73–86. https://doi.org/10.1016/j.envint.2011.10.002

    Article  CAS  PubMed  Google Scholar 

  3. Kümmerer K, Haiß A, Schuster A, Hein A, Ebert I (2016) Antineoplastic compounds in the environment—substances of special concern. Environ Sci Pollut Res 23:14791–14804. https://doi.org/10.1007/s11356-014-3902-8

    Article  CAS  Google Scholar 

  4. Cristóvão M, Janssens R, Yadav A, Pandey S, Luis P, Van der Bruggen B, Dubey K, Mandal M, Crespo J, Pereira V (2020) Predicted concentrations of anticancer drugs in the aquatic environment: what should we monitor and where should we treat? J Hazard Mater. https://doi.org/10.1016/j.jhazmat.2020.122330

    Article  PubMed  Google Scholar 

  5. Ferrando-Climent L, Rodriguez-Mozaz S, Barceló D (2014) Incidence of anticancer drugs in an aquatic urban system: from hospital effluents through urban wastewater to natural environment. Environ Pollut 193:216–223. https://doi.org/10.1016/j.envpol.2014.07.002

    Article  CAS  PubMed  Google Scholar 

  6. Isidori M, Lavorgna M, Russo C, Kundi M, Žegura B, Novak M, Filipič M, Mišík M, Knasmueller S, de Alda ML (2016) Chemical and toxicological characterisation of anticancer drugs in hospital and municipal wastewaters from Slovenia and Spain. Environ Pollut 219:275–287. https://doi.org/10.1016/j.envpol.2016

    Article  CAS  PubMed  Google Scholar 

  7. Azuma T (2018) Distribution of Anticancer Drugs in River Waters and Sediments of the Yodo River Basin, Japan. Appl Sci 8:2043. https://doi.org/10.3390/app8112043

    Article  CAS  Google Scholar 

  8. Martín J, Camacho-Muñoz D, Santos JL, Aparicio I, Alonso E (2014) Occurrence and ecotoxicological risk assessment of 14 cytostatic drugs in wastewater. Water Air Soil Pollut 225:1896. https://doi.org/10.1007/s11270-014-1896-y

    Article  CAS  Google Scholar 

  9. Orias F, Perrodin Y (2013) Characterisation of the ecotoxicity of hospital effluents: a review. Sci Total Environ 454:250–276. https://doi.org/10.1016/j.scitotenv.2013.02.064

    Article  CAS  PubMed  Google Scholar 

  10. Zhang J, Chang VW, Giannis A, Wang JY (2013) Removal of cytostatic drugs from aquatic environment: a review. Sci Total Environ 445:281–298. https://doi.org/10.1016/j.scitotenv.2012.12.061

    Article  CAS  PubMed  Google Scholar 

  11. Yadav A, Pandey S, Mandal MK, Dubey KK (2020) Development of cost-effective RP-HPLC methods for detection of cyclophosphamide, etoposide and paclitaxel. Sep Sci Plus. https://doi.org/10.1002/sscp.201900071

    Article  Google Scholar 

  12. Elersek T, Milavec S, Korošec M, Brezovsek P, Negreira N, Zonja B, de Alda ML, Barceló D, Heath E, Ščančar J (2016) Toxicity of the mixture of selected antineoplastic drugs against aquatic primary producers. Environ Sci Pollut Res 23:14780–14790. https://doi.org/10.1007/s11356-015-6005-2

    Article  CAS  Google Scholar 

  13. Russo C, Lavorgna M, Česen M, Kosjek T, Heath E, Isidori M (2018) Evaluation of acute and chronic ecotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and UV treated samples. Environ Pollut 233:356–363. https://doi.org/10.1016/j.envpol.2017.10.066

    Article  CAS  PubMed  Google Scholar 

  14. Česen M, Eleršek T, Novak M, Žegura B, Kosjek T, Filipič M, Heath E (2016) Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures. Environ Pollut 210:192–201. https://doi.org/10.1016/j.envpol.2015.12.017

    Article  CAS  PubMed  Google Scholar 

  15. Lutterbeck CA, Wilde ML, Baginska E, Leder C, Machado ÊL, Kümmerer K (2016) Degradation of cyclophosphamide and 5-fluorouracil by UV and simulated sunlight treatments: assessment of the enhancement of the biodegradability and toxicity. Environ Pollut 208:467–476. https://doi.org/10.1016/j.envpol.2015

    Article  CAS  PubMed  Google Scholar 

  16. Parrella A, Lavorgna M, Criscuolo E, Russo C, Isidori M (2015) Eco-genotoxicity of six anticancer drugs using comet assay in daphnids. J Hazard Mater 286:573–580. https://doi.org/10.1016/j.jhazmat.2015.01.012

    Article  CAS  PubMed  Google Scholar 

  17. Białk-Bielińska A, Mulkiewicz E, Stokowski M, Stolte S, Stepnowski P (2017) Acute aquatic toxicity assessment of six anti-cancer drugs and one metabolite using biotest battery–biological effects and stability under test conditions. Chemosphere 189:689–698. https://doi.org/10.1016/j.chemosphere.2017.08.174

    Article  CAS  PubMed  Google Scholar 

  18. Kumar M, Jaiswal S, Sodhi KK, Shree P, Singh DK, Agrawal PK, Shukla P (2019) Antibiotics bioremediation: perspectives on its ecotoxicity and resistance. Environ Int 124:448–461. https://doi.org/10.1016/j.envint.2018.12.065

    Article  CAS  PubMed  Google Scholar 

  19. Dubey KK, Luke GA, Knox C, Kumar P, Pletschke BI, Singh PK, Shukla P (2018) Vaccine and antibody production in plants: developments and computational tools. Brief Funct Genom 17:295–307. https://doi.org/10.1093/bfgp/ely020

    Article  CAS  Google Scholar 

  20. Huang G-J, Deng J-S, Chen C-C, Huang C-J, Sung P-J, Huang SS, Kuo Y-H (2014) Methanol extract of Antrodia camphorata protects against lipopolysaccharide-induced acute lung injury by suppressing NF-κB and MAPK pathways in mice. J Agric Food Chem 62:5321–5329. https://doi.org/10.1021/jf405113g

    Article  CAS  PubMed  Google Scholar 

  21. Dangi AK, Sinha R, Dwivedi S, Gupta SK, Shukla P (2018) Cell line techniques and gene editing tools for antibody production: a review. Front Pharmacol 9:630. https://doi.org/10.3389/fphar.2018.00630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang C-Y, Ju D-T, Chang C-F, Reddy PM, Velmurugan BK (2017) A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer. Biomedicine 7:12–23. https://doi.org/10.1051/bmdcn/2017070423

    Article  Google Scholar 

  23. Simsek C, Esin E, Yalcin S (2019) Metronomic chemotherapy: a systematic review of the literature and clinical experience. J Oncol 2019:5483791. https://doi.org/10.1155/2019/5483791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Das MT, Budhraja V, Mishra M, Thakur IS (2012) Toxicological evaluation of paper mill sewage sediment treated by indigenous dibenzofuran-degrading Pseudomonas sp. Bioresour Technol 110:71–78. https://doi.org/10.1016/j.biortech.2012.01.078

    Article  CAS  PubMed  Google Scholar 

  25. Lojk J, Repas J, Veranič P, Bregar VB, Pavlin M (2020) Toxicity mechanisms of selected engineered nanoparticles on human neural cells in vitro. Toxicology. https://doi.org/10.1016/j.tox.2020.152364

    Article  PubMed  Google Scholar 

  26. Parrella A, Kundi M, Lavorgna M, Criscuolo E, Russo C, Isidori M (2014) Toxicity of exposure to binary mixtures of four anti-neoplastic drugs in Daphnia magna and Ceriodaphnia dubia. Aquat Toxicol 157:41–46. https://doi.org/10.1016/j.aquatox.2014.09.012

    Article  CAS  PubMed  Google Scholar 

  27. Kovács R, Bakos K, Urbányi B, Kövesi J, Gazsi G, Csepeli A, Appl ÁJ, Bencsik D, Csenki Z, Horváth Á (2016) Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish. Environ Sci Pollut Res 23:14718–14729. https://doi.org/10.1007/s11356-015-5036-z

    Article  CAS  Google Scholar 

  28. CDER F (1996) Guidance for industry: single dose acute toxicity testing for pharmaceuticals (Final)

  29. Russo C, Lavorgna M, Piscitelli C, Isidori M (2020) Toxicity of anticancer drug residues in organisms of the freshwater aquatic chain. Fate and effects of anticancer drugs in the environment. Springer, Cham, pp 379–401. https://doi.org/10.1007/978-3-030-21048-9_15

    Chapter  Google Scholar 

  30. Zounková R, Odráška P, Doležalová L, Hilscherová K, Maršálek B, Bláha L (2007) Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals. Environ Toxicol Chem 26(10):2208–2214. https://doi.org/10.1897/07-137R.1

    Article  PubMed  Google Scholar 

  31. Grung M, Källqvist T, Sakshaug S, Skurtveit S, Thomas KV (2008) Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline. Ecotox Environ Safe 71(2):328–340. https://doi.org/10.1016/j.ecoenv.2007.10.015

    Article  CAS  Google Scholar 

  32. Parrella A, Lavorgna M, Criscuolo E, Russo C, Fiumano V, Isidori M (2014) Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans. Chemosphere 115:59–66. https://doi.org/10.1016/j.chemosphere.2014.01.013

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by Department of Biotechnology (Ministry of Science and Technology), Govt. of India [Grant No: BT/IN/INNO-INDIGO/26/MKM/2015-16]. We would also like to acknowledge Dr. Vinod Yadav (Assistant Professor, Department of Microbiology, Central University of Haryana) for guidance during experiment.

Funding

This work was financially supported by Department of Biotechnology (Ministry of Science and Technology), Govt. of India [Grant No: BT/IN/INNO-INDIGO/26/MKM/2015-16].

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Authors and Affiliations

  1. Bioprocess Engineering Laboratory, Department of Biotechnology, Central University of Haryana, Mahendergarh, Haryana, 123031, India

    Ankush Yadav & Kashyap Kumar Dubey

  2. Department of Chemical Engineering, National Institute of Technology Durgapur, Durgapur, West-Bengal, 713029, India

    Mrinal Kanti Mandal

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  1. Ankush Yadav
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Yadav, A., Mandal, M.K. & Dubey, K.K. In Vitro Cytotoxicity Study of Cyclophosphamide, Etoposide and Paclitaxel on Monocyte Macrophage Cell Line Raw 264.7. Indian J Microbiol 60, 511–517 (2020). https://doi.org/10.1007/s12088-020-00896-1

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