{"title":"Overcoming Drug Resistance: P-Gp Inhibitor Verapamil Enhances Temozolomide’s Antiproliferative Effect in Neuroblastoma Cells","authors":"Mustafa Karademir, Ahmet Altun","doi":"10.1134/s1819712424010082","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Neuroblastoma is one of the most common and deadly childhood solid tumors. P-glycoprotein (P-gp) pump plays a role in developing resistance to many chemotherapeutic agents. The high expression of P-gp is associated with poor prognosis in drug resistance and neuroblastoma treatment. We aimed to evaluate the anticancer effect of Temozolomide (TMZ) on the SH-SY5Y human neuroblastoma cell line in the presence of P-gp inhibitor Verapamil (VER). In the present study, the antiproliferative effect of TMZ on SH-SY5Y cells alone and in combination with VER was evaluated using a colorimetric XTT viability test.SH-SY5Y cells were seeded to 96 well plates at 10 000 cells/well. TMZ (100 µM–10 mM) and VER (0.25–10 µg/mL) were applied to the cells alone first, then XTT measurements were performed after 24 and 48 h. In the study’s second phase, VER was applied to the cells at the fixed concentration of 2.5 µg/mL to block P-gp pumps, then increasing concentrations of TMZ were applied to the cells in the presence of VER. The current study showed that in addition to cytotoxic effects, VER + TMZ administration accelerated apoptosis in SH-SY5Y cells compared to TMZ utilization alone. The wound healing assay demonstrated that VER + TMZ combination also inhibited cell migration. Considering this evidence, combining TMZ with VER in the neuroblastoma cell line may inhibit migration and cell proliferation via the apoptosis pathway and produce a substantial anticancer effect.</p>","PeriodicalId":19119,"journal":{"name":"Neurochemical Journal","volume":null,"pages":null},"PeriodicalIF":0.5000,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1134/s1819712424010082","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Neuroblastoma is one of the most common and deadly childhood solid tumors. P-glycoprotein (P-gp) pump plays a role in developing resistance to many chemotherapeutic agents. The high expression of P-gp is associated with poor prognosis in drug resistance and neuroblastoma treatment. We aimed to evaluate the anticancer effect of Temozolomide (TMZ) on the SH-SY5Y human neuroblastoma cell line in the presence of P-gp inhibitor Verapamil (VER). In the present study, the antiproliferative effect of TMZ on SH-SY5Y cells alone and in combination with VER was evaluated using a colorimetric XTT viability test.SH-SY5Y cells were seeded to 96 well plates at 10 000 cells/well. TMZ (100 µM–10 mM) and VER (0.25–10 µg/mL) were applied to the cells alone first, then XTT measurements were performed after 24 and 48 h. In the study’s second phase, VER was applied to the cells at the fixed concentration of 2.5 µg/mL to block P-gp pumps, then increasing concentrations of TMZ were applied to the cells in the presence of VER. The current study showed that in addition to cytotoxic effects, VER + TMZ administration accelerated apoptosis in SH-SY5Y cells compared to TMZ utilization alone. The wound healing assay demonstrated that VER + TMZ combination also inhibited cell migration. Considering this evidence, combining TMZ with VER in the neuroblastoma cell line may inhibit migration and cell proliferation via the apoptosis pathway and produce a substantial anticancer effect.
期刊介绍：
Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components.
The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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