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Amaç: Kurkumin, Curcuma longa bitkisinden izole edilen ve literatürde anti-kanser etkiye sahip olduğu bilinen bir polifenoldür. Kurkuminin, meme kanserinde MAPK ve PI3K sinyal yolaklarında etkisine dair çalışmalar bulunmasına rağmen, TGF-β sinyali üzerinde etkisine dair bir çalışma mevcut değildir. Bu kapsamda, mevcut çalışmada kurkuminin iki farklı alt tip [MCF-7 (Luminal A) ve MDA-MB-231 (triple negatif)] meme kanseri ve HUVEC kontrol hücrelerinde TGF-β sinyalinin düzenlenmesinde rol alan GSK-3β, Smad4 ve CCDN1 genlerinde ekspresyon seviyesinde etkisinin belirlenmesi amaçlanmıştır. Materyal ve Method: Kurkuminin MCF-7, MDA-MB-231 ve HUVEC hücrelerinde GSK-3β, Smad4 ve CCDN1 genlerinin ekspresyon seviyelerinde değişimlerin belirlenmesi için, kurkuminin etkin dozu belirlendikten sonra, kurkumin uygulanan hücrelerden RNA izole edilerek ilgili genlerin ekspresyon seviyeleri RT-PCR ile analiz edilmiştir. Bulgular: WST-1 bulgularına göre meme kanseri hücrelerinde en etkin doz olarak belirlenen 10 µM kurkumin uygulanan MCF-7, MDA-MB-231 ve HUVEC hücrelerinde GSK-3β ekspresyon seviyeleri sırasıyla 6.1-, 15.0- ve 7.6- kat iken, Smad4 ekspresyon seviyelerinin 1.7-, 5.1- ve 8.9-kat arttığı belirlenmiştir (p<0.05). Ayrıca, 10 µM kurkumin uygulanan MCF-7, MDA-MB-231 ve HUVEC hücrelerinde CCDN1 mRNA seviyesinin sırasıyla 7.6-, 3.8- ve 8.6- kat artığı tespit edilmiştir. Sonuç: Sonuç olarak, kurkumin meme kanseri hücrelerinde TGF- β temelli sinyal yolaklarının düzenlenmesinde rol almaktadır. Ayrıca, kurkuminin daha agresif özelliğe sahip olan MDA-MB-231 hücrelerinde azalan CCDN1 seviyesine bağlı olarak, MCF-7 hücrelerine göre GSK-3β ve Smad4 ‘ün ekspresyon seviyelerinde daha fazla kat artışına neden olduğu tespit edilmiştir. Ancak, kurkuminin meme kanseri hücrelerinde TGF-β temelli Smad4 ve diğer sinyal yolaklarında etkisinin belirlenmesine yönelik daha ileri moleküler analizlerin gerçekleştirilmesi gereklidir.
Purpose: Curcuma is a polyphenol that is isolated from the Curcuma longa plant and is known to have anti-cancer effects in literature. Although studies have been found on the effect of curcumin on the MAPK and PI3K signal pathways in breast cancer, there is no study on its effect on the TGF-β signal. In this context, the current study aimed at determining the expression level of curcumin in two different subtypes [MCF-7 (Luminal A) and MDA-MB-231 (triple negative)] of breast cancer and TGF-β signal regulation in HUVEC control cells in the GSK-3β, Smad4 and CCDN1 genes. Materials and Methods: To determine changes in the expression levels of the GSK-3β, Smad4 and CCDN1 genes in curcumin MCF-7, MDA-MB-231 and HUVEC cells, after the effective dose of curcumin is determined, the expression levels of the relevant genes are analysed by RT-PCR by isolating the RNA from the applicable cells of curcumin. Results: According to the WST-1 findings, the levels of expression of GSK-3β in MCF-7, MDA-MB-231 and HUVEC cells of 10 μM curcumin, which is determined as an effective dose in breast cancer cells, were identified as 6.1-, 15.0- and 7.6-fold, while the levels of expression of Smad4 increased 1.7-, 5.1- and 8.9-fold respectively (p<0.05). Furthermore, the levels of CCDN1 mRNA in MCF-7, MDA-MB-231 and HUVEC cells applied to 10 μM curcumin have been detected increased 7.6, 3.8 and 8.6 times, respectively. Result: As a result, curcumin plays a role in regulating TGF- β-based signal pathways in breast cancer cells. Furthermore, due to the decrease of CCDN1 levels in the MDA-MB-231 cells that curcumin has more aggressive properties, it has been found that GSK-3β and Smad4 have more than MCF-7 cells caused an increase in expression levels. However, further molecular analyses are required to determine the effect of kurkumin on the TGF-β-based Smad4 and other signal pathways in breast cancer cells.
Aim: Curcumin is a polyphenol extracted from the Curcuma longa plant known for its anti-cancer properties in the literature. Although the effects of curcumin on the MAPK and PI3K signaling pathways in breast cancer are known, its effect on the TGF-β signaling pathways has not been identified. In this context, our study aimed to determine the effects of curcumin on gene expression levels of GSK-3β, Smad4 and CCDN1, which regulate the TGF-β signaling pathway, in two different subtypes of breast cancer [MCF-7 (Luminal A) and MDA-MB-231 (triple-negative)], and HUVEC control cell lines. Materials and method: First, the effective concentration of curcumin was determined using WST-1 viability assay to investigate its effects on GSK-3β, Smad4 and CCDN1gene expression levels in MCF-7, MDA-MB-231, and HUVEC cell lines. Subsequently, RNA was isolated from cells treated with curcumin, and gene expression levels were analyzed by RT-PCR. Results: 10 µM curcumin was the most effective concentration in MCF-7 and MDA-MB-231 breast cancer cell lines according to WST-1 results. Our results showed a 6.1-, 15.0-, and 7.6- fold increase in GSK-3β expression levels and a 1.7-, 5.1-, and 8.9-fold increase in Smad4 expression levels in MCF-7, MDA-MB-231, and HUVEC cell lines, respectively. Additionally, 7.6-, 3.8- and 8.6-fold increase in CCDN1 mRNA levels were detected in MCF-7, MDA-MB-231 and HUVEC cells, respectively following 10 µM curcumin incubation.
Alan : Sağlık Bilimleri
Dergi Türü : Uluslararası
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