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Journals / Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi / 2026 / Cilt: 59 Sayı: 2

Controlled Direct-Current Electric Field Exposure Reshapes Glioma Cell Stress Biology and Motility Within a Redox-Responsive Adaptive Window: An Exploratory In Vitro Study

Doğru Akım Elektrik Alanı Glioma Hücrelerinde Stres Biyolojisi ve Motiliteyi Redoks-Yanıtlı Adaptif Pencerede Yeniden Şekillendirir: In Vitro Çalışma

Berkay Ayhan(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, ANKARA SAĞLIK UYGULAMA VE ARAŞTIRMA MERKEZİ)0000-0001-9746-1492
Mehmet Emre Yıldırım(UNIVERSITY OF HEALTH SCIENCES, ANKARA HEALTH RESEARCH CENTER)0000-0001-7039-2706
Pages
99–106
Publication Date
2026-09-04
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This platform provides an exploratory, hypothesis-generating framework for studying controlled bioelectric regulation of glioma stress biology rather than nonspecific tumor ablation.

📌 3 Key Takeaways

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Objective & Hypothesis:AIM: This exploratory in vitro study examined whether controlled direct-current electric field (dcEF) exposure modulates glioma cell behavior through a restricted redox-responsive adaptive window rather than nonspecific cytotoxicity, focusing on proliferation, apoptosis, oxidative stress, and motility.
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Key Findings & Data:MATERIAL AND METHOD: Human glioblastoma cell lines U87MG and U251, together with glioma stem cell–like (GSC-like) sphere cultures, were exposed to dcEFs using a biophysically validated platform approximating low-intensity electric field magnitudes reported during clinical transcranial direct current stimulation (tDCS).
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Conclusion & Impact:This platform provides an exploratory, hypothesis-generating framework for studying controlled bioelectric regulation of glioma stress biology rather than nonspecific tumor ablation.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:glioma · doğru akım elektrik alanı · oksidatif stres

Abstract

AIM: This exploratory in vitro study examined whether controlled direct-current electric field (dcEF) exposure modulates glioma cell behavior through a restricted redox-responsive adaptive window rather than nonspecific cytotoxicity, focusing on proliferation, apoptosis, oxidative stress, and motility. MATERIAL AND METHOD: Human glioblastoma cell lines U87MG and U251, together with glioma stem cell–like (GSC-like) sphere cultures, were exposed to dcEFs using a biophysically validated platform approximating low-intensity electric field magnitudes reported during clinical transcranial direct current stimulation (tDCS). The platform employed agar–saline bridges, COMSOL-based electric-field validation, and continuous thermal monitoring to minimize electrolysis, direct electrode contact, and thermal stress. Cells were stimulated at 100, 200, or 300 µA for 30 min/day over five consecutive days. Outcomes included viability (MTT), apoptosis (Annexin V/PI), intracellular ROS (DCFDA), migration, and invasion. ROS dependency was assessed using N-acetylcysteine (NAC). To distinguish specific motility suppression from generalized membrane damage, lactate dehydrogenase (LDH) release and live-cell normalized migration/invasion analyses were performed. RESULTS: dcEF exposure produced dose-dependent effects most prominent in U87MG cells. At 200 µA, a coordinated response emerged—moderate oxidative perturbation (+45% ROS), partial viability reduction (78%), and marked motility suppression (migration 38%; invasion 35%)—without overt LDH-defined cytotoxicity (12.8%). Live-cell normalized analysis confirmed that motility suppression exceeded viability loss. In contrast, 300 µA appeared to exceed this adaptive range, producing generalized cytotoxic stress (LDH 34.5%). NAC pretreatment attenuated ROS accumulation and apoptosis and partially rescued viability-adjusted motility, supporting a ROS-dependent contribution. U251 cells showed comparable responses, while GSC-like cultures exhibited attenuated oxidative and apoptotic responses. CONCLUSION: The findings support a threshold-dependent, redox-responsive model of dcEF exposure, in which biologically effective stimulation appears to occur within a restricted stress-adaptive range before transitioning into generalized cytotoxicity at higher intensities. This platform provides an exploratory, hypothesis-generating framework for studying controlled bioelectric regulation of glioma stress biology rather than nonspecific tumor ablation.

Özet

AMAÇ: Bu çalışmada, kontrollü in vitro doğru akım elektrik alanı (dcEF) uygulamasının glioma hücrelerinde proliferasyon, apoptoz, oksidatif stres ve motilite üzerindeki etkileri; biyolojik olarak etkin stimülasyonun sınırlı bir stres-adaptif pencere içinde gerçekleşip gerçekleşmediğini sınamak amacıyla eksploratif bir tasarımda incelendi. GEREÇ VE YÖNTEM: İnsan glioblastoma hücre hatları U87MG ve U251 ile glioma kök hücre benzeri (GSC-like) küresel kültürler; klinik transkraniyal doğru akım stimülasyonunda (tDCS) bildirilen düşük yoğunluklu elektrik alan büyüklüklerini taklit eden, agar–salin köprüleri ile elektrokimyasal artefakttan izole edilmiş, COMSOL ile saha doğrulaması ve sürekli termal izlem uygulanan biyofiziksel olarak doğrulanmış bir platformda dcEF’ye maruz bırakıldı. Hücrelere ardışık beş gün boyunca günde 30 dk süreyle 100, 200 veya 300 µA uygulandı. Hücre canlılığı (MTT), apoptoz (Annexin V/PI), hücre içi ROS (DCFDA), migrasyon ve invazyon değerlendirildi. ROS bağımlılığı N-asetilsistein (NAC) ön tedavisi ile araştırıldı. Spesifik motilite baskılanmasını yaygın membran hasarından ayırmak için laktat dehidrojenaz (LDH) salınım testi ve canlı-hücre normalize migrasyon/invazyon analizi yapıldı. BULGULAR: dcEF uygulaması özellikle U87MG hücrelerinde belirgin doza bağımlı etkiler oluşturdu. 200 µA koşulu; orta düzeyde oksidatif perturbasyon (+%45 ROS), kısmi canlılık azalması (%78) ve belirgin motilite baskılanması (migrasyon %38, invazyon %35) ile karakterize bir koordineli biyolojik yanıt oluştururken, yaygın hücresel kollaps kanıtı izlenmedi (LDH %12,8). 300 µA koşulu adaptif aralığı aşan, yaygın sitotoksisite-baskın bir referans durum olarak yorumlandı (LDH %34,5). NAC ön tedavisi 200 µA’da hem ROS hem apoptotik yanıtı azaltarak canlı-hücre normalize motiliteyi belirgin biçimde restore etti. U251 hücrelerinde benzer yanıtlar gözlenirken GSC-like kültürlerde oksidatif ve apoptotik yanıtlar daha zayıftı. SONUÇ: Bulgular, dcEF uygulamasının eşik bağımlı, redoks-yanıtlı bir modelle uyumlu olduğunu; biyolojik olarak etkin stimülasyonun, daha yüksek yoğunluklarda jeneralize sitotoksisiteye geçmeden önce sınırlı bir stres-adaptif aralıkta gerçekleştiğini desteklemektedir. Bu çalışma, doğrudan tümör ablasyonu yerine kontrollü biyoelektrik stres modülasyonu çerçevesinde glioma biyolojisinin yeniden şekillendirilmesi için bir deneysel platform sunmaktadır.

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Cite This Article

Ayhan, B., Yıldırım, M. E. (2026). Controlled Direct-Current Electric Field Exposure Reshapes Glioma Cell Stress Biology and Motility Within a Redox-Responsive Adaptive Window: An Exploratory In Vitro Study. Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi, Cilt: 59 Sayı: 2, 99–106. https://doi.org/10.20492/aeahtd.1952896

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