Oleandrin Downregulates Toll-Like Receptor Pathway Genes in Human Endometrial Carcinoma Cells

Yıl 2025, Cilt: 7 Sayı: 3 , 372 - 381 , 31.12.2025

Sedef Akçaalan , Canan Eroğlu Güneş , Fatma Seçer Çelik , Ercan Kurar

https://doi.org/10.47112/neufmbd.2025.99

https://izlik.org/JA98SD97XZ

Öz

Endometrial cancer arises from the development of malignant cells in endometrial tissues and ranks as the sixth most prevalent neoplasm among women globally. Toll-like receptors (TLRs), as part of the innate immune system, have a key function in the detection of pathogens. Previous research has previously indicated an association between TLRs and different types of cancers, highlighting the role of TLR expression in cancer cells in relation to progression, apoptosis, and survival. Nerium oleander L., a member of the Apocynaceae family, has been traditionally employed in addressing various diseases. Oleandrin, a compound obtained from the leaves and seeds of N. oleander, has been shown to suppress the growth of various human cancer cells. This study aimed to examine the impact of oleandrin on TLR pathway genes in Ishikawa human endometrial carcinoma cells. Following oleandrin treatment, XTT proliferation assay was conducted at the 24., 48. and 72. hours. The IC50 value was found to be 75.3 nM at the 48 hour. The impact of oleandrin on the expression levels of TLRs (1-10) and MYD88 genes in Ishikawa cells was analyzed using qPCR. Oleandrin administration caused a notable decrease in the expression levels of TLR1, TLR6 and MYD88, whereas the expression of other TLRs remained relatively stable. In conclusion, oleandrin exhibited cytotoxic effects, significantly decreasing the viability of Ishikawa cancer cells and influencing the TLR signaling cascade through modulation of the levels of TLR1, TLR6, and MYD88 genes.

Anahtar Kelimeler

Endometrial carcinoma , Oleandrin , Toll like receptors

Etik Beyan

This article is the revised and developed version of the unpublished conference presentation entitled “A Cardiac Glycoside of Nerium oleander L. Downregulates TLR1, TLR6 and MYD88 Genes in Human Endometrial Carcinoma Cells”, orally presented at the Second International Congress on Biological and Health Sciences-2022”.

Oleandrin, İnsan Endometriyal Karsinom Hücrelerinde Toll Benzeri Reseptör Yolağı Genlerinin İfadesini Baskılar

https://izlik.org/JA98SD97XZ

Öz

Endometrial kanser, endometriyal dokularda kötü huylu hücrelerin gelişiminden kaynaklanır ve dünya genelinde kadınlar arasında altıncı en yaygın kanser türüdür. Doğuştan gelen bağışıklık sisteminin bir bileşeni olan Toll benzeri reseptörler (TLR’ler), patojenlerin tanınmasında kritik bir işlev üstlenir. Önceki araştırmalar, TLR’ler ile farklı kanser türleri arasında bir ilişki olduğunu ve TLR ekspresyonunun kanser hücrelerinde progresyon, apoptoz ve hayatta kalma ile ilişkili olduğunu göstermiştir. Apocynaceae familyasından olan Nerium oleander L., geleneksel olarak çeşitli hastalıkların tedavisinde kullanılmıştır. N. oleander’in yaprakları ve tohumlarından elde edilen oleandrin bileşiği, çeşitli insan kanser hücrelerinin büyümesini baskıladığı gösterilmiştir. Bu çalışma, oleandrinin Ishikawa insan endometrial karsinom hücrelerinde TLR yolağı genleri üzerine etkisini incelemeyi amaçlamıştır. Oleandrin uygulamasının ardından, XTT proliferasyon testi 24., 48. ve 72. saatlerde gerçekleştirilmiştir. IC50 değeri 48. saat için 75,3 nM olarak belirlenmiştir. Oleandrinin TLR’ler (1-10) ve MYD88 genlerinin ekspresyon seviyeleri üzerindeki etkisi qPCR ile analiz edilmiştir. Oleandrin uygulaması sonucunda TLR1, TLR6 ve MYD88 genlerinin ekspresyon seviyelerinde belirgin bir azalma ile sonuçlanırken, diğer TLR’lerin ifadesi nispeten stabil kalmıştır. Sonuç olarak, oleandrin, Ishikawa kanser hücrelerinin canlılığını önemli ölçüde azaltarak, TLR1, TLR6 ve MYD88 genlerinin seviyelerinin modülasyonu yoluyla TLR sinyal yolaklarını etkileyen sitotoksik etkiler göstermiştir.

Anahtar Kelimeler

Endometriyal karsinom , Oleandrin , Toll benzeri reseptörler

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