INVESTIGATION OF ANTIANGIOGENIC AND APOPTOTIC EFFECTS OF GALANTAMINE OBTAINED FROM LEUCOJUM AESTIVUM ON MCF-7 BREAST CANCER CELL LINE

Yıl 2023, Cilt: 24 Sayı: 4, 457 - 465, 09.10.2023

Ali Tarık İnce , Doç. Dr. Funda Karabağ , İbrahim Bulduk

https://doi.org/10.18229/kocatepetip.1178657

Öz

OBJECTIVE: The current study aims to investigate the antiangiogenic and apoptotic effects of galantamine in breast cancer cells and to add new information to the literature.
MATERIAL AND METHODS: In this study, MCF-7 breast cancer cell line was used and galantamine was obtained from Leucojum aestivum by HPLC method. The effect of galantamine on cell viability was determined by CCK-8 assay at 9 different doses (control, 10, 40, 70, 100, 130, 160, 190, 210 μg/ml) including the control group. Then, to understand the effect of galantamine, other assays (total antioxidant status (TAS), total oxidant status (TOS), poly-ADP ribose polymerase (PARP), and vascular endothelial growth factor (VEGF) levels) were examined in 3 groups; control, LD50 (100 μg/ml) and high dose (210 μg/ml) group. The oxidative stress index (OSI) was then calculated.
RESULTS: Galantamine decreased cell viability. The LD50 dose was determined as 100 μg/ml. There was no significant change in VEGF levels. There was a significant dose-dependent decrease in PARP levels (Control: 2.78667±0.155392, LD50: 1.51000±0.107145, High dose: 1.01000±0.054772 ng/L, p=0.000). Compared to the control group, there was a significant dose-related decrease in TAS data (Control: 0.09633±0.002658, LD50: 0.06283±0.002317, High dose: 0.04050±0.001871, p=0.000) and a significant dose-related increase in TOS data (Control: 0.12500±0.010488, LD50: 0.21667±0.015055, High dose: 0.31833±0.021370, p=0.000). A significant dose-related increase in OSI data was found. (Control: 129.964±13.018, LD50: 345.161±26.480, High dose: 788.485±78.575, p=0.000).
CONCLUSIONS: It was determined that galantamine had no significant effect on angiogenesis at any dose based on VEGF levels. Galantamine had a negative effect on cell viability and proliferation at certain doses to MCF-7 cells and was found to increase oxidative stress. The decrease in PARP levels indicates the possibility that cells may result in an apoptotic process. These findings may be useful to take a different approach to the use of galantamine in cancer research.

Anahtar Kelimeler

Galantamine, Oxidative Stress, Poly (ADP-ribose) polymerase, Vascular endothelial growth factor, MCF-7 cells

MCF-7 MEME KANSERİ HÜCRE HATTINDA LEUCOJUM AESTIVUM'DAN ELDE EDİLEN GALANTAMİNİN ANTİANJİOJENİK VE APOPTOTİK ETKİLERİNİN ARAŞTIRILMASI

Öz

AMAÇ: Mevcut çalışma, MCF-7 meme kanseri hücrelerinde galantaminin antianjiojenik ve apoptotik etkilerini araştırmayı ve literatüre yeni bir bilgi kazandırmayı amaçlamaktadır.
GEREÇ VE YÖNTEM: Bu çalışmada, MCF-7 meme kanseri hücre dizisi kullanılmış ve galantamin, Leucojum aestivum'dan HPLC yöntemi ile elde edilmiştir. Galantaminin hücre canlılığı üzerindeki etkisi, kontrol grubu dahil 9 farklı dozda (kontrol, 10, 40, 70, 100, 130, 160, 190, 210 μg/ml) CCK-8 tahlili ile belirlendi. Daha sonra galantaminin etkisini anlamak için diğer analizler (toplam antioksidan seviyesi (TAS), toplam oksidan seviyesi (TOS), poli-ADP riboz polimeraz (PARP) ve vasküler endotelyal büyüme faktörü (VEGF) seviyeleri) 3 grupta incelendi; kontrol, LD50 (100 μg/ml) ve yüksek doz (210 μg/ml) grubu. Ardından oksidatif stres endeksi (OSI) hesaplandı.
BULGULAR: Galantamin hücre canlılığını azalttı. LD50 dozu 100 μg/ml olarak belirlendi. VEGF düzeylerinde herhangi anlamlı bir değişim olmadığı belirlendi. PARP düzeylerinde doza bağlı olarak anlamlı bir azalma olmuştur (Kontrol: 2.78667±0.155392, LD50: 1.51000±0.107145, Yüksek doz: 1.01000±0.054772 ng/L, p=0.000). Kontrol grubuna kıyasla TAS verilerinde doza bağlı anlamlı bir azalma (Kontrol: 0.09633±0.002658, LD50: 0.06283±0.002317, Yüksek doz: 0.04050±0.001871, p=0.000) ve TOS verilerinde doza bağlı anlamlı bir artış vardı (Kontrol:0.12500±0.010488, LD50: 0.21667±0.015055, Yüksek doz: 0.31833±0.021370, p=0.000). OSI verilerinde doza bağlı anlamlı artış bulundu. (Kontrol: 129.964±13.018, LD50: 345.161±26.480, Yüksek doz: 788.485±78.575, p=0.000).
SONUÇ: Galantaminin herhangi bir dozda VEGF düzeyleri baz alınarak anjiyogenezde anlamlı bir etkisinin olmadığı belirlendi. Galantaminin MCF-7 hücrelerine belirli dozlarda hücre canlılığına negatif etki yapmıştır ve oksidatif stresi artırdığı bulunmuştur. PARP seviyelerindeki düşüş hücrelerin apoptotik süreçle sonuçlanabileceği ihtimalini göstermektedir. Bu bulgular, kanser araştırmalarında galantamin kullanımına farklı bir yaklaşım getirmek için faydalı olabilir.

Anahtar Kelimeler

Galantamin, Oksidatif stres, Poli (ADP-riboz) polimeraz, Vasküler endotelyal büyüme faktörü, MCF-7 hücreleri

Kaynakça

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