HL-60 ve THP-1 Hücrelerinde Eskulin’in İndüklediği Apoptoz ve Lösemi Yüzey Belirteçlerinin Baskılanması: Potansiyel Seçici Bir Antikanser Ajan

Yıl 2024, Cilt: 46 Sayı: 6, 933 - 944, 07.11.2024

Neslihan Meriç , Cansu Özbayer

https://doi.org/10.20515/otd.1543538

Öz

Esas olarak Cortex fraxini'den türetilen doğal bir kumarin bileşiği olan eskülin, anti-inflamatuar ve antioksidan özellikleriyle bilinir. Hematolojik kanser türlerinden biri olan lösemi, beyaz kan hücrelerinin kontrolsüz çoğalmasıyla karakterizedir ve yüksek ölüm oranlarına sahiptir. Bu çalışmada, eskülinin (Eskületin-6-Glukozid) lösemi hücre hatları üzerindeki potansiyel antikanser etkilerini araştırmayı amaçladık ve bu bileşiğin apoptotik yollarla kanser tedavisinde nasıl kullanılabileceğine odaklandık. Deneylerimizde akut promyelositik lösemi (HL-60) ve akut monositik lösemi (THP-1) hücre hatları kullanıldı. Kanser hücresi sayımı ve canlılık analizleri MTS testi (5-(3-karboksimetoksifenil)-2-(4,5-dimetiltiazol)-3-(4-sülfofenil) tetrazolyum iç tuz testi) kullanılarak gerçekleştirildi. Apoptozis, FITC etiketli Annexin V ve propidyum iyodür kullanılarak değerlendirildi. Kaspaz-3 aktivasyonu, sitokrom C salınımı, lösemi hücre yüzey belirteçleri ve mitokondriyal membran potansiyeli (MMP) akış sitometrisi ile analiz edildi. Sonuçlarımız eskülinin lösemi hücre hatlarında apoptozu indükleyebileceğini gösterdi. Ek olarak, lösemi yüzey belirteçleri tedavi sonrası her iki hücre hattında da tedavi sonrası istatistiksel olarak anlamlı şekilde azaldı. HL-60 ve THP-1 hücreleri MMP, Kaspaz-3 ve Sitokrom C aktiviteleri açısından farklı hücresel tepkiler gösterdi; HL-60 hücreleri eskülin tedavisine daha dirençliyken, THP-1 hücreleri daha duyarlıydı. Bu bulgular eskülinin apoptotik yolları hedefleyerek kanser tedavisinde potansiyel bir ajan olabileceğini düşündürmektedir. Ancak eskülinin antikanser etkilerini tam olarak anlamak için daha fazla in vivo çalışma ve klinik öncesi modellemeye ihtiyaç vardır. Farklı kanser tiplerine karşı etkinliğinin değerlendirilmesi bu bileşiğin terapötik potansiyelini daha da genişletebilir.

Anahtar Kelimeler

Esculin, Lösemik Hücreler, Apoptozis, Yüzey İşaretleyicileri

Destekleyen Kurum

Kütahya Sağlık Bilimleri - BAP

Proje Numarası

133

Esculin-Induced Apoptosis and Suppression of Leukemia Surface Markers in HL-60 and THP-1 Cells: A Potential Selective Anticancer Agent

Öz

Esculin, a natural coumarin compound primarily derived from Cortex fraxini, is known for its anti-inflammatory and antioxidant properties. Leukemia, a type of hematological cancer, is characterized by the uncontrolled proliferation of white blood cells and has high mortality rates. In this study, we aimed to investigate the potential anticancer effects of esculin (Esculetin-6-Glucoside) on leukemia cell lines, focusing on how this compound could be utilized in cancer treatment through apoptotic pathways. Our experiments used acute promyelocytic leukemia (HL-60) and acute monocytic leukemia (THP-1) cell lines. Cancer cell counting and viability analyses were conducted using the MTS assay(5-(3-carboxymethoxyphenyl)-2-(4,5-dimethylthiazol)-3-(4-sulfophenyl) tetrazolium inner salt assay). Apoptosis was assessed using FITC-labeled Annexin V and propidium iodide. Caspase-3 activation, cytochrome C release, leukemia cell surface markers, and mitochondrial membrane potential (MMP) were analyzed via flow cytometry. Our results demonstrated that esculin can induce apoptosis in leukemia cell lines. Additionally, leukemia surface markers post-treatment were statistically significantly reduced post-treatment in both cell lines. HL-60 and THP-1 cells exhibited different cellular responses in terms of MMP, Caspase-3, and Cytochrome C activities; HL-60 cells were more resistant to esculin treatment, while THP-1 cells were more sensitive. These findings suggest that esculin could become a potential agent in cancer treatment by targeting apoptotic pathways. However, more in vivo studies and preclinical modeling are needed to understand the anticancer effects of esculin fully. Evaluating its efficacy against different cancer types could further expand the therapeutic potential of this compound.

Anahtar Kelimeler

Esculin, Leukemic Cells, Apoptosis, Surface Markers

Proje Numarası

133

Kaynakça

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