Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments

<i>Background Objectives:</i> The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) an...

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Main Authors: Andreea M. Kis, Ioana Macasoi, Corina Paul, Matilda Radulescu, Roxana Buzatu, Claudia G. Watz, Adelina Cheveresan, Delia Berceanu, Iulia Pinzaru, Stefania Dinu, Aniko Manea, Marioara Poenaru, Claudia Borza, Cristina A. Dehelean
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1648-9144/58/2/167
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author Andreea M. Kis
Ioana Macasoi
Corina Paul
Matilda Radulescu
Roxana Buzatu
Claudia G. Watz
Adelina Cheveresan
Delia Berceanu
Iulia Pinzaru
Stefania Dinu
Aniko Manea
Marioara Poenaru
Claudia Borza
Cristina A. Dehelean
author_facet Andreea M. Kis
Ioana Macasoi
Corina Paul
Matilda Radulescu
Roxana Buzatu
Claudia G. Watz
Adelina Cheveresan
Delia Berceanu
Iulia Pinzaru
Stefania Dinu
Aniko Manea
Marioara Poenaru
Claudia Borza
Cristina A. Dehelean
author_sort Andreea M. Kis
collection DOAJ
description <i>Background Objectives:</i> The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. <i>Materials and Methods:</i> The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). <i>Results</i>: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. <i>Conclusions</i>: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.
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spelling doaj.art-4a1b918cbca0486fa439d64c34d527652023-11-23T20:59:03ZengMDPI AGMedicina1010-660X1648-91442022-01-0158216710.3390/medicina58020167Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo AssessmentsAndreea M. Kis0Ioana Macasoi1Corina Paul2Matilda Radulescu3Roxana Buzatu4Claudia G. Watz5Adelina Cheveresan6Delia Berceanu7Iulia Pinzaru8Stefania Dinu9Aniko Manea10Marioara Poenaru11Claudia Borza12Cristina A. Dehelean13Department of ENT, “Victor Babeş” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaDepartament of Toxicology and Drug Industry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timişoara, RomaniaDepartment of Pediatrics, “Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaDepartment of Microbiology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartment of Dental Aesthetics, Faculty of Dental Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 9 No., Revolutiei Bv., 300041 Timişoara, RomaniaResearch Center for Pharmaco-Toxicological Evaluations, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartment of Pharmacology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartment of Microbiology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartament of Toxicology and Drug Industry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timişoara, RomaniaDepartment of Pedodontics, Faculty of Dental Medicine, “Victor Babeş” University of Medicine and Pharmacy Timisoara, 9 No., Revolutiei Bv., 300041 Timişoara, RomaniaDepartment of Neonatology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartment of ENT, “Victor Babeş” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timișoara, RomaniaDepartment of Pathophysiology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, RomaniaDepartament of Toxicology and Drug Industry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timişoara, Romania<i>Background Objectives:</i> The neoplastic process remains a major health problem facing humanity. Although there are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. Methotrexate (Met) and Cetuximab (Cet) are two basic chemotherapeutics used in cancer practice, but notwithstanding despite many years of use, the mechanisms by which the multitude of side-effects occur are not yet fully understood. Thus, the present study focused on the in vitro and in ovo evaluation of the associated toxic mechanisms on keratinocytes, keys cells in the wound healing process. <i>Materials and Methods:</i> The two chemotherapeutics were tested in eight different concentrations to evaluate keratinocytes viability, the anti-migratory effect, and the influence on the expression of markers involved in the production of cell apoptosis. In addition, the potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM). <i>Results</i>: The results revealed that Met induced decreased cell viability as well as increased expression of pro-apoptotic genes. In the vascular plexus of the chorioallantoic membrane, Met caused vascular irritation accompanied by capillary hemorrhage and vascular stasis. <i>Conclusions</i>: Summarizing, Cet presents a safer toxicological profile, compared to Met, based on the results obtained from both in vitro (cell viability, wound healing, RT-PCR assays), and in ovo (HET-CAM assay) techniques.https://www.mdpi.com/1648-9144/58/2/167methotrexatecetuximabHaCaTcell viabilityHET-CAM assayRT-PCR
spellingShingle Andreea M. Kis
Ioana Macasoi
Corina Paul
Matilda Radulescu
Roxana Buzatu
Claudia G. Watz
Adelina Cheveresan
Delia Berceanu
Iulia Pinzaru
Stefania Dinu
Aniko Manea
Marioara Poenaru
Claudia Borza
Cristina A. Dehelean
Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
Medicina
methotrexate
cetuximab
HaCaT
cell viability
HET-CAM assay
RT-PCR
title Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
title_full Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
title_fullStr Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
title_full_unstemmed Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
title_short Methotrexate and Cetuximab—Biological Impact on Non-Tumorigenic Models: In Vitro and In Ovo Assessments
title_sort methotrexate and cetuximab biological impact on non tumorigenic models in vitro and in ovo assessments
topic methotrexate
cetuximab
HaCaT
cell viability
HET-CAM assay
RT-PCR
url https://www.mdpi.com/1648-9144/58/2/167
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