JUGLONUN PANKREAS KANSERİ HÜCRELERİNDE PROGRAMLI HÜCRE ÖLÜMÜNÜ İNDÜKLEYEREK GÖSTERDİĞİ ANTİKANSER ETKİSİ

Yıl 2023, Cilt: 4 Sayı: 2, 321 - 332, 21.09.2023

Dudu Erkoç Kaya , Duygu Dursunoğlu

Öz

Amaç: Pankreas kanseri (PK), belirti vermeden ileri düzeye kadar sessiz seyri ile kötü prognoza sahiptir. Ek olarak, halihazırda sınırlı olan tedavi seçenekleri, alternatif tedavi stratejileri ve teröopatik ajanların geliştirilmesini zorunlu kılmaktadır. Kanser için yeni terapötik ajanları araştırmak amacıyla yapılan araştırmalarda doğal ürünler temel kaynaklardır. Bunların arasında doğal bir naftokinon olan Juglon, kanser hücrelerinde sitotoksik etkisi, apoptoz ve otofajiyi indüklemesi, antianjiyogenez ve kanser hücresi göçünü engellemesi ile öne çıkmaktadır. Bu nedenle çalışmamızda juglonun BxPC-3 Pankreas kanseri hücreleri üzerindeki antikanser aktivitesini ve apoptotik etkilerini araştırmayı amaçladık.
Yöntem: Apoptotik etkileri değerlendirmek için; proapoptotik Bax, antiapoptotik Bcl-2 ve önemli apoptoz inhibitörü Birc5 (Survivin) gen ekspresyonları qPCR analizi ile belirlendi. Annexin V-FITC ile immünofloresan analizi yaparak apoptoz sonuçlarını da doğruladık.
Bulgular: qPCR analizine göre juglon, 10, 15 ve 20µM dozlarda Bax gen ekspresyonlarında sırasıyla 2,24, 1,57, 2,43 kat düzeyinde istatistiksel olarak anlamlı artışlara neden oldu. Bcl-2 gen ekspresyonu için, juglon tedavilerinden sonra 20µM doz dışındaki diğer uygulamalarda düşük kat artışları saptadık. Bu değişiklikler istatistiksel olarak anlamlı değildi. Juglon, tüm tedavi dozlarında survivin gen ekspresyonunu azaltırken, 20 μM juglon uygulmasındaki 2.39 kat azalma istatistiksel olarak anlamlıydı. qPCR analizine ek olarak, juglonun BxPC-3 hücrelerinde doza bağlı olarak apoptozu arttırdığını immünofloresan analizi ile doğruladık.
Sonuç: Gen ekspresyonu ve immünfloresans analizinin tüm sonuçları birlikte ele alındığında, çalışmamız juglonun pankreas kanseri hücrelerinde muhtemelen intrinsik apoptotik yolu indükleyerek antikanser aktivite gösterdiğini ortaya koymuştur.

Anahtar Kelimeler

JUGLON, PANKREAS KANSERİ, APOPTOZ, BAX GENİ, BCL-2 GENİ, SURVIVIN GENİ

Destekleyen Kurum

Çalışma için herhangi bir destek alınmamıştır

THE ANTICANCER ACTIVITY OF JUGLONE VIA INDUCING PROGRAMMED CELL DEATH IN PANCREATIC CANCER CELLS

Öz

Aim: Pancreatic cancer (PC), has a poor prognosis with its silent course until the advanced level without any symptoms. Additionally, currently limited treatment options makes developing alternative treatment strategies and agents mandatory. In researches conducted to investigate new therapeutic agents for cancer natural products are main sources. Among all, Juglone, a natural naphthoquinone, stands out with its cytotoxic effect in cancer cells, induction of apoptosis and autophagy, inhibition of antiangiogenesis and cancer cell migration. Thus, in our study, we aimed to investigate the anticancer activity and the apoptotic effects of juglone on BxPC-3 Pancreatic cancer cells.
Method: To evaluate the apoptotic effects; proapoptotic Bax, antiapoptotic Bcl-2 and an important inhibitor of apoptosis Birc5 (Survivin) gene expressions were determined by qPCR analysis. We also confirmed the results for apoptosis by performing immunofluorescence analysis using Annexin V-FITC.
Findings: According to qPCR analysis, juglone induced statistically significant 2.24, 1.57, 2.43 fold increases of Bax gene the expressions at 10, 15 and 20µM doses, respectively. We detected low fold increases after juglone treatments for Bcl-2 gene expression at other treatments except 20µM dose. This changes were not statistically significant. Juglone decreased survivin gene expression at all treatment doses while 2.39 fold decrease at 20 μM doses of juglone was statistically significant. Also, we confirmed clearly by the immunofluorescence analysis that juglone increased apoptosis dose-dependently in BxPC-3 cells.
Results: Taken together all the results of gene expression and immunfloresence analysis our study suggests that juglone shows anticancer activity by inducing apoptosis possibly enhancing intrinsic apoptotic pathway in Pancreatic cancer cells.
Keywords: juglone, pancreatic cancer, Bax gene, Bcl-2 gene, survivin gene, apoptosis,

Anahtar Kelimeler

juglone, pancreatic cancer, Bax gene, Bcl-2 gene, survivin gene, apoptosis

Kaynakça

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