Dinamik 3B Meme Tümörü Modelinde Oleuropein Kanser Köklülüğünü Azaltmaktadır

Abstract

Kanser kök hücrelerinin (KKH) tümör mikro çevresiyle etkileşiminin araştırılması,çeşitli hücresel ve moleküler adaptasyon mekanizmaları aracılığıyla anjiyogenez ve metastazı desteklemedeki rollerine dair önemli bilgiler sağlar. Bu çalışmada, oleuropein (OLE) ile hedefli tedaviden sonra KKH'lerin biyolojik yanıtlarını üç boyutlu (3B) bir mikro çevrede değerlendirmeyi amaçladık. Sferoid yapılarda apoptotik aktiviteyi değerlendirmek için TUNEL testi kullanıldı. OLE tedavisinin ardından, hem statik hem de dinamik kültürler OCT3/4, NANOG, SOX2, SURVIVIN, CYCLIN-D1 ve p21 ekspresyonunun arttığını RT-qPCR ile gösterdik. Bu bulgular topluca, OLE'nin kök hücreler üzerindeki anti-proliferatif ve pro-apoptotik etkilerini vurgulamaktadır.

Keywords

• Meme kanseri
• MCF-7
• kök hücre
• oleuropein

Oleuropein Inhibits Cancer Stemness in a Dynamic 3D Breast Tumor Model

Abstract

Investigating the interaction of cancer stem cells (CSCs) with the tumor microenvironment provides critical insights into their roles in promoting angiogenesis and metastasis through various cellular and molecular adaptation mechanisms, including survival, maintenance of stemness, dormancy, and treatment response. In the present study, we aimed to evaluate the biological responses of CSCs following targeted treatment with phenolic oleuropein (OLE), a glycosylated seco-iridoid compound, within a three-dimensional (3D) microenvironment. CD44⁺/CD24⁻/low CSCs were isolated from the MCF-7 cell line using magnetic-activated cell sorting (MACS). The expression levels of stemness-related genes (OCT3/4, NANOG, SOX2) and drug resistance markers (ABCG1, ABCG2) were assessed in both MCF-7 cells and CSCs using RT-qPCR and the spheroid structures were further evaluated using the TUNEL assay to assess apoptotic activity. CSCs exhibited significantly elevated expression of ABCG1 and stemness markers (OCT3/4, NANOG, SOX2) compared to parental MCF-7 cells. Following OLE treatment, both static and dynamic cultures demonstrated increased expression of OCT3/4, NANOG, SOX2, SURVIVIN, CYCLIN-D1, and p21. Notably, while untreated cells expressed ABCG1 and ABCG2, these genes were not detectable in OLE-treated cells under either culture condition. Collectively, these findings underscore the anti-proliferative and pro-apoptotic effects of OLE on CSCs and highlight its potential to counteract drug resistance mechanisms within a biomimetic 3D microenvironment.

Keywords

• Breast cancer
• MCF-7
• stem cell
• oleuropein

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