Yalçın ERZURUMLU, Hatice Kübra DOĞAN, Deniz ÇATAKLI

ZERDEÇALIN BİYOAKTİF BİLEŞİĞİ KURKUMİN, GEMSİTABİNİN PROSTAT KANSERİ HÜCRELERİNDEKİ ANTİ-MALİGNANT ÖZELLİĞİNİ GELİŞTİREBİLİR

Amaç: Bu çalışmanın amacı kurkuminin gemsitabinin prostat kanseri hücreleri üzerindeki antikanser özelliklerine olan olası sinerjistik etkisinin araştırılmasıdır. Gereç ve Yöntem: Çalışmalarda insan prostat adenokarsinoma hücre hattı LNCaP kullanıldı. Gemsitabin ve kurkuminin birlikte uygulanmasının LNCaP hücrelerinin canlılığı üzerindeki etkisi WST-1 yöntemiyle araştırıldı. Otofaji, ubikitin-proteazom sistemi (UPS), katlanmamış protein yanıtı (UPR) ve hücre ölümü ile ilişkili proteinler, androjenik sinyal, proto-onkojenik, anjiyojenik ve epitelyal-mezankimal geçiş (EMT) ile ilişkili protein düzeyleri immünoblotlama çalışmaları ile incelendi. Sonuç ve Tartışma: Sonuçlarımız kurkuminin gemsitabinin LNCaP hücreleri üzerindeki anti kanser etkilerini güçlendirdiğini gösterdi. Kurkumin ve gemsitabinin eş uygulaması gemsitabinin hücre canlılığı üzerindeki baskılayıcı etkisini güçlendirdi. Bununla birlikte eş uygulamanın otofajiyi düzenlediği, UPS ve UPR’yi daha güçlü uyardığı, androjenik sinyali baskıladığı, hücre ölümü ile ilişkili PARP-1 ve kaspaz-3 aktivasyonuna yol açtığı, proto-onkojenik c-Myc, anjiyojenik VEGF-A ifade düzeylerini güçlü şekilde baskıladığını gösterdi. Ayrıca eş uygulamanın E-kaderin ifadesini uyararak ve N-kaderin düzeyini baskılayarak EMT’yi negatif düzenlediği belirlendi. Bu sonuçlar, gemsitabin ve kurkuminin birlikte kullanımının, gemsitabinin antikanser etkilerini geliştirerek prostat kanserine yönelik güçlü bir terapötik yaklaşım sunabileceğini düşündürmektedir.

Anahtar Kelimeler:

Gemsitabin, katlanmamış protein yanıtı, kurkumin, otofaji, prostat kanseri

CURCUMIN, THE BIOACTIVE COMPOUND OF TURMERIC, MAY IMPROVE THE ANTI-MALIGNANT PROPERTY OF GEMCITABINE IN PROSTATE CANCER CELLS

Objective: The aim of this study was to investigate the possible synergistic effect of curcumin on the anticancer features of gemcitabine on prostate cancer cells. Material and Method: The human prostate adenocarcinoma cell line LNCaP was used in the studies. The effect of the co-administration of gemcitabine and curcumin on the viability of LNCaP cells was investigated by the WST-1 assay. Autophagy, ubiquitin-proteasome system (UPS), unfolded protein response (UPR) and cell death-associated proteins, androgenic signaling, proto-oncogenic, angiogenic and epithelial-mesenchymal transition (EMT) associated protein levels were investigated by immunoblotting studies. Result and Discussion: Our results showed that curcumin potentiated the anticancer effects of gemcitabine on LNCaP cells. Co-administration of curcumin and gemcitabine strengthened the suppressive effect of gemcitabine on cell viability. Moreover, co-administration modulated the autophagy, more strongly stimulated UPS and UPR, suppressed androgenic signaling, led to the activation of cell death-related poly [ADP-ribose] polymerase 1 (PARP-1) and caspase-3 and strongly suppressed the expression levels of proto-oncogenic c-Myc and angiogenic vascular endothelial growth factor-A (VEGF-A). In addition, it was determined that co-administration negatively regulated EMT by stimulating E-cadherin expression and suppressing N-cadherin level. These results suggest that the combined usage of gemcitabine and curcumin may offer a potent therapeutic approach for prostate cancer by enhancing the anticancer effects of gemcitabine.

Keywords:

Autophagy, curcumin, gemcitabine, unfolded protein response, prostate cancer,

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