med j west black sea

Medical Journal of Western Black Sea

2822-4302 2587-0602

Zonguldak Bulent Ecevit University

10.29058/mjwbs.1743485

Medical Physiology (Other)

Tıbbi Fizyoloji (Diğer)

Betülinik asit EAG1 Baskılanması Yoluyla SH-SY5Y Nöroblastom Hücrelerinde Apoptoz ve G2/M Hücre Döngüsü Durmasını İndükler

Betulinic Acid Induces Apoptosis and G2/M Cell Cycle Arrest in SH-SY5Y Neuroblastoma Cells via EAG1 Suppression

https://orcid.org/0000-0001-6333-7784

Yalçınkaya

Tuğba

T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü Mikrobiyoloji Referans Laboratuvarları ve Biyolojik Ürünler Dairesi Başkanlığı

https://orcid.org/0000-0002-4581-1945

Kaya

Şeyda

BULENT ECEVIT UNIVERSITY, ZONGULDAK AHMET ERDOGAN VOCATIONAL SCHOOL OF HEALTH SCIENCES

https://orcid.org/0000-0002-2148-7351

Yildiz

Hatice Kubra

ANKARA YILDIRIM BEYAZIT UNIVERSITY, INSTITUTE OF HEALTH SCIENCES, CANCER BIOLOGY (DR)

https://orcid.org/0000-0003-1584-0072

Çarhan

Ahmet

ANKARA YILDIRIM BEYAZIT UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF BASIC MEDICAL SCIENCES (MEDICINE), DEPARTMENT OF MEDICAL BIOLOGY

08 31 2025

9 2 274 284 07 16 2025 08 21 2025

2017

Medical Journal of Western Black Sea

Amaç: Nöroblastoma, çocuklarda en sık görülen ekstrakraniyal solid tümör olup özellikle ileri evrelerde yüksek mortaliteye sahiptir.Tekrarlama ve ilaç direnci gibi mevcut tedavi yöntemlerinin sınırlılıkları nedeniyle, tümöre özgü etkisi yüksek ve normal hücrelere minimumtoksisite gösteren yeni ajanlara ihtiyaç vardır. Doğal bir pentasiklik triterpen olan betulinik asit (BA), seçici antitümör özellikleri nedeniyle ilgiçekmektedir.Gereç ve Yöntemler: Bu çalışmada, BA’nın SH-SY5Y nöroblastoma ve epitelyal hücre hattı, Vero, üzerindeki sitotoksik ve moleküler etkileriincelendi. Hücre canlılığı ise MTT testi ile değerlendirildi. Morfolojik değişiklikler mikroskop ile gözlemlendi. Apoptoz (Bax, Bcl-2, Caspase-3,p53, p21) ve hücre döngüsü (CDK1, Cyclin B1, Ki-67, EAG1) ile ilişkili genlerin ekspresyon seviyeleri qPCR ile analiz edildi.Bulgular: BA, her iki hücre hattında da zaman ve doz bağımlı olarak hücre canlılığını anlamlı şekilde azalttı; SH-SY5Y hücreleri dahaduyarlı bulundu (48 saat için IC₅₀=75 μM). SH-SY5Y hücrelerinde hücre büzülmesi ve hücre yoğunluğunda azalma gibi morfolojikdeğişiklikler belirgindi. Bu hücre hattında BA tedavisi pro-apoptotik genlerin (Bax, Caspase-3, p53, p21) ifadesini artırırken, anti-apoptotik veproliferasyonla ilişkili genlerin (Bcl-2, CDK1, Cyclin B1, Ki-67, EAG1) ifadesini azalttı (p

Aim: Neuroblastoma is the most common extracranial solid tumour in children and is associated with high mortality, particularly in advancedstages. Given the limitations of current treatment approaches, such as recurrence and drug resistance, novel agents with tumour-specificeffects and minimal toxicity to normal cells are needed. Betulinic Acid (BA), a naturally occurring pentacyclic triterpene, has gained attentiondue to its selective antitumor properties.Material and Methods: This study investigated the cytotoxic and molecular effects of BA on SH-SY5Y neuroblastoma and epithelialcell lines, Vero. Cell viability was assessed using the MTT assay. Microscopic observations were conducted to evaluate morphologicalchanges. Quantitative real-time PCR (qPCR) was performed to analyse the gene expression changes associated with apoptosis (Bax, Bcl-2,Caspase-3, p53, p21) and the cell cycle (CDK1, Cyclin B1, Ki-67, EAG1).Results: BA significantly reduced cell viability in both cell lines in a time- and dose-dependent manner, with SH-SY5Y cells showing greatersensitivity (IC₅₀=75 μM at 48 hours). Morphological changes such as cell shrinkage and reduced cell density were more pronounced inSH-SY5Y cells. In this cell line, BA treatment significantly upregulated pro-apoptotic genes (Bax, Caspase-3, p53, p21) and downregulatedanti-apoptotic and proliferation-related genes (Bcl-2, CDK1, Cyclin B1, Ki-67, EAG1) (p

Betulinic acid neuroblastoma SH-SY5Y apoptosis cell cycle EAG1

Betulinik asit nöroblastoma SH-SY5Y apoptoz hücre döngüsü EAG1

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