Transcriptome analysis displays new molecular insights into the mechanisms of action of Mebendazole in gastric cancer cells.

Autor: da Silva EL; Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Cel. Nunes de Melo, Fortaleza, Brazil., Mesquita FP; Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Cel. Nunes de Melo, Fortaleza, Brazil., Pinto LC; Laboratory of Experimental Neuropathology, Biological Science Institute, Federal University of Pará, Mundurucus Street, Belém, Brazil., Gomes BPS; Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SAMAM), Evandro Chagas Institute (IEC), Ananindeua, Brazil., de Oliveira EHC; Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SAMAM), Evandro Chagas Institute (IEC), Ananindeua, Brazil., Burbano RMR; Molecular Biology Laboratory, Ophir Loyola Hospital, Av. Governador Magalhães Barata, Belém, Brazil; Laboratory of Human Cytogenetics, Institute of Biological Sciences, Federal University of Pará, Augusto Correa Avenue, Belém, Brazil., de Moares MEA; Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Cel. Nunes de Melo, Fortaleza, Brazil., de Souza PFN; Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Cel. Nunes de Melo, Fortaleza, Brazil; Visiting Researcher at the Cearense Foundation to Support Scientific and Technological Development, Brazil; National Institute of Science and Technology in Human Pathogenic Fungi, Ribeirão Preto, Brazil. Electronic address: pedrofilhobio@gmail.com., Montenegro RC; Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Cel. Nunes de Melo, Fortaleza, Brazil; Red Latinoamericana de Implementación y Validación de guias clinicas Farmacogenomicas (RELIVAF), Brazil. Electronic address: rcm.montenegro@gmail.com.
Jazyk: angličtina
Zdroj: Computers in biology and medicine [Comput Biol Med] 2024 Nov 19; Vol. 184, pp. 109415. Date of Electronic Publication: 2024 Nov 19.
DOI: 10.1016/j.compbiomed.2024.109415
Abstrakt: Gastric cancer (GC) is a common cancer worldwide. Therefore, searching for effective treatments is essential, and drug repositioning can be a promising strategy to find new potential drugs for GC therapy. For the first time, we sought to identify molecular alterations and validate new mechanisms related to Mebendazole (MBZ) treatment in GC cells through transcriptome analysis using microarray technology. Data revealed 1066 differentially expressed genes (DEGs), of which 345 (2.41 %) genes were upregulated, 721 (5.04 %) genes were downregulated, and 13,231 (92.54 %) genes remained unaltered after MBZ exposure. The overexpressed genes identified were CCL2, IL1A, and CDKN1A. In contrast, the H3C7, H3C11, and H1-5 were the top 3 underexpressed genes. Gene set enrichment analysis (GSEA) identified 8 pathways significantly overexpressed in the treated group (p < 0.05 and FDR<0.25). The validation of the expression of top desregulated genes by RT-qPCR confirmed the transcriptome results, where MBZ increased the CCL2, IL1A, and CDKN1A and reduced the H3C7, H3C11, and H1-5 transcript levels. Expression analysis in samples from TCGA databases correlated that the lower ILI1A and higher H3C11 and H1-5 gene expression are associated with decreased overall survival rates in patients with GC, indicating that MBZ treatment can improve the prognosis of patients. Thus, the data demonstrated that the drug MBZ alters the transcriptome of the AGP-01 lineage, mainly modulating the expression of histone proteins and inflammatory cytokines, indicating a possible epigenetic and immunological effect on tumor cells, these findings highlight new mechanisms of action related to MBZ treatment. Additional studies are still needed to better clarify the epigenetic and immune mechanism of MBZ in the therapy of GC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Ltd.)
Databáze: MEDLINE
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