Abstract
Background Objectives: 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. Materials and Methods: 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). Results: 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. Conclusions: 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.
Highlights
Worldwide, over 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually [1]
To evaluate the effect induced by both cytostatics (Methotrexate and Cetuximab) on human immortalized keratinocytes (HaCaT), the Alamar blue colorimetric test was performed by employing a stimulation time of 24 h
When the human immortalized keratinocytes were treated with the same concentrations (5, 15, 25, 30, 60, 90 μg/mL) of Methotrexate, the humanimmortalized immortalizedkeratinocytes keratinocytes (HaCaT) cells manifested a dose-dependent viability decrease, as follows: 89%, 83.2%, 80%, 76.4%, 74.89%, and 70.02%, respectively
Summary
Over 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually [1]. A suitable drug option in advanced cases is Methotrexate (Met)—a folic acid antagonist which acts as a ligand for the folate receptor, that has been associated with abnormally rapid cell growth and exhibits anti-inflammatory and immunosuppressant activities, being used for long-term treatment schemes in leukemia and rheumatic diseases and advanced cancer head and neck treatment [4]. There are currently different therapeutic options, they raise a multitude of shortcomings related to the toxic effects associated with their administration. 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. Materials and Methods: 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. The potential irritating effect on the vascular plexus were highlighted by applying the in ovo method, chick chorioallantoic membrane (HET-CAM)
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