Emine Merve DEMİRBAŞ BÜYÜKTÜT, Dudu ERKOÇ KAYA, Fatma GÖKTÜRK, Hilal ARIKOĞLU

Juglon, PANC-1 ve BxPC-3 Pankreas Kanser Hücre Hatlarında Hücre Büyümesi, Hayatta Kalma ve Metabolizmada Merkezi Rol Oynayan mTOR Gen İfadesine İki Yönlü Etki Eder

Arkaplan/Hedefler: Bir naftakinon olarak juglonun çeşitli kanser hücrelerinde sitotoksik ve apoptotik etkisi gösterilmiş, daha önceki araştırmalarımızda PANC-1 ve BxPC-3 hücrelerinde bu etkilerinin yanı sıra anti-invaziv ve anti-metastatik etki gösterdiği rapor edilmiştir. Bu çalışmada kanser hücrelerinin sağkalımı, metastaz ve tedaviye direnç gelişmesi süreçlerinde merkezi rolü olan mitokondrial biyogenez ve aktivasyon ile ilişkili anahtar proteinleri kodlayan GRP75, TFAM ve mTOR genleri üzerine juglonun etkileri PANC-1 ve BxPC-3 pankreas kanseri hücre hatlarında araştırılmıştır. Metodlar: Çalışmamızda MTT testi sonuçlarından elde edilen IC50 değeri dikkate alınarak 5, 10, 15 ve 20 μM juglon dozları uygulama dozu olarak seçilmiş ve juglonun belirlenen dozlardaki 24 saatlik uygulamasından sonra hedef genlerin ifadeleri qPCR yöntemiyle incelenmiştir. Bulgular: Çalışma sonuçlarımız, juglonun her iki hücre hattında da mTOR ekspresyonu üzerinde zıt ve güçlü bir etkiye sahip olduğunu ortaya koydu. Sonuç: Çalışma bulgularımız, hücresel homeostazda, hücre büyümesi, hayatta kalması ve metabolizması dahil olmak üzere bir dizi hücresel olayda merkezi rol oynayan mTOR ifadesi üzerindeki bu etkileri ile juglonun geliştirilebilir bir potansiyele sahip olduğu ve pankreas kanseri ile savaşta yeni stratejiler için umut vaad eden bir teröpotik ajan olduğu düşüncemizi desteklemektedir.

Anahtar Kelimeler:

Juglone, Pancreatic cancer, Mitochondrial biogenesis, mTOR gene expression

Juglone Effects by Dual Way on mTOR Gene Expression, Which Plays Central Role in Cell Growth, Survival and Metabolism, in PANC-1 and BxPC-3 Pancreatic Cancer Cell Lines

Background/Aims: Juglone, as a naphthoquinone, has been shown to have cytotoxic and apoptotic effects in various cancer cells and besides this effects it was reported to have anti-invasive and anti-metastatic effects in PANC-1 and BxPC-3 cells in our previous studies. In this study, we investigated the effects of juglone on GRP75, TFAM and mTOR genes encoding key proteins associated with mitochondrial biogenesis and activation in PANC-1 and BxPC-3 pancreatic cancer cells since mitochondria has central roles in cancer cell survival, metastasis and therapeutic resistance. Methods: In our study; 5, 10, 15 and 20 μM juglone doses were selected as the application doses considering the IC50 value determined after MTT test results and the expressions of the target genes were analyzed by qPCR method after application of juglone doses for 24 hours. Results: Our study results revealed that juglone had an opposite and strong effects on mTOR expression in both cell lines. Conclusion: Our findings suggest that juglone has a developable potential and is a promising theurapeutic agent to develop new strategies for the battle with cancer with those effects on mTOR gene which plays a central role in cellular homeostasis and several cellular events including cell growth, survival and metabolism.

Keywords:

Juglone, Pancreatic cancer, Mitochondrial biogenesis, mTOR gene expression,

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