Kalkon Bileşiklerinin Prostat Kanseri Hücrelerinde Antiproliferatif ve Nekroptotik Etkilerinin Belirlenmesi

Öz

Kanser, genetik ve çevresel koşullar ile hücrelerin kontrolsüz bölünmesi ve çoğalmasıyla ortaya çıkan çok basamaklı ölümcül bir hastalıktır. Prostat kanseri, erkekleri etkileyen ve küresel olarak erkeklerde artan ölüm oranlarına önemli ölçüde katkıda bulunan malignitelerden biridir. Prostat kanserinde, uzun bir hastalık geçmişi, genetik-fenotipik çeşitlilik ve hastaların klinik ilerlemesindeki belirsizlik nedeniyle yeni yaklaşımların geliştirilmesi gerekliliği ortaya çıkmaktadır. Kalkonlar, bitkilerde bulunan, farmakolojik aktif bileşiklerdir. Doğal ya da sentetik kalkon türevlerinin kanser hücrelerinde anti-kanser aktiviteye sahip olduğu gözlenmiştir. Mevcut çalışmada, sentezi ve karakterizasyonu yapılmış iki kalkon türevinin (Bileşik 1 ve Bileşik 2) anti-kanser ve anti-proliferatif etkileri insan prostat kanseri hücre soylarında (LNCaP ve PC-3) araştırıldı. Bileşiklerin hücre canlılığı üzerindeki anti-proliferatif etkisi 48 saatlik tedavi sonrası SRB canlılık analizi ile değerlendirildi. Kalkon bileşiklerinin sitotoksik etkilerinden sorumlu hücre ölüm modunu belirlemek amacıyla floresan boyama (Hoechst 33342+Anneksin-V+Propidyum iyodür) yöntemi ve gen ekspresyonlarında meydana getirdiği değişiklikleri saptamak için de RT-PCR analizi gerçekleştirildi. Bileşiklerin, LNCaP ve PC-3 hücrelerinde doza ve zamana bağlı olarak anti-proliferatif etkileri saptandı. Üçlü floresan boyama sonucu ile bileşiklerin LNCaP ve PC-3 hücrelerinde sekonder apoptozisi teşvik ettiği tespit edildi. Hücre ölümü yolak genleri BCL-2, MLKL, FAS ve PARP ekspresyon seviyelerinde anlamlı artışlar belirlendi. Elde edilen sonuçların ışığında, Bileşik 1 ve Bileşik 2’nin prostat kanserinde anti-proliferatif etki gösterdiği ve nekroptozisi indüklediği sonucuna varıldı.

Anahtar Kelimeler

• Prostat kanseri
• Kalkonlar
• Antiproliferatif
• Antikanser
• Nekroptozis

Determination of Antiproliferative and Necroptotic Effects of Chalcone Compounds on Prostate Cancer Cells

Öz

Cancer is a multistage fatal disease that occurs with genetic and environmental conditions and uncontrolled division and proliferation of cells. Prostate cancer is one of the malignancies that affects men and contributes significantly to the increasing mortality rates in men globally. Due to a long disease history, genetic-phenotypic diversity, and uncertainty in the clinical progression of patients in prostate cancer, the necessity of developing new approaches arises. Chalcones are pharmacologically active compounds found in plants. It has been observed that natural or synthetic chalcone derivatives have anti-cancer activity in cancer cells. In the current study, the anti-cancer and anti-proliferative effects of two synthesized and characterized chalcone derivatives (Compound 1 and Compound 2) were investigated in human prostate cancer cell lines (LNCaP and PC-3). The anti-proliferative effect of the compounds on cell viability was assessed by SRB viability assay after 48 hours of treatment. Fluorescent staining (Hoechst 33342+Annexin-V+Propidium iodide) method was used to determine the cell death mode responsible for the cytotoxic effects of chalcone compounds, and RT-PCR analysis was performed to determine the changes in gene expressions. Anti-proliferative effects of the compounds were detected in LNCaP and PC-3 cells in a dose- and time-dependent manner. It was determined by triple fluorescent staining that the compounds induced secondary apoptosis in LNCaP and PC-3 cells. Significant increases in expression levels of cell death pathway genes BCL-2, MLKL, FAS and PARP were determined. In the light of the results obtained, it was concluded that Compound 1 and Compound 2 showed anti-proliferative effect and induced necroptosis in prostate cancer.

Anahtar Kelimeler

• Prostate cancer
• Chalcones
• Antiproliferative
• Anticancer
• Necroptosis

Kaynakça

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