Paronychia kurdica’nın metanolik ve sulu ekstraktlarının pankreas kanser hücrelerinde in vitro antioksidan, sitotoksik, apoptotik ve anti-migrasyon etkileri

Abstract

Pankreas kanseri, hızlı metastaz ve tedavi direnci nedeniyle en ölümcül malignitelerden biridir; tanı sonrası metastaz riski yüksek, beş yıllık sağkalım oranları ise düşüktür. Bu çalışmada, Paronychia kurdica ekstraktlarının fenolik ve flavonoid içerikleri, antioksidan kapasiteleri ve pankreas kanseri hücreleri üzerindeki biyolojik etkileri araştırılmıştır. Metanolik (MeOH) ekstrakt, sulu ekstrakta kıyasla daha yüksek toplam fenolik (26,39 mg GAE/g) ve flavonoid (21,52 mg QE/g) içerik göstermiş ve DPPH ile FRAP analizlerine göre orta düzeyde antioksidan etki sergilemiştir. LC–MS analizi, her iki ekstrakta da klorojenik asit, rutin, ferulik asit ve p-kumarik asidin bulunduğunu ortaya koymuş, MeOH ekstraktında rutin düzeyinin daha yüksek olduğu belirlenmiştir. Her iki ekstrakt da MIA PaCa-2 hücrelerinde doza bağlı sitotoksisite göstermiştir (IC₅₀: MeOH 411,4 µg/mL, sulu ekstrakt 385,5 µg/mL). Scratch analizleri, MeOH ekstraktının hücre göçünü %50,56–70,14 oranında inhibe ettiğini göstermiştir. Apoptotik mekanizmalar, qRT-PCR ve Western blot analizleri ile doğrulanmış; özellikle MeOH ekstraktı ile muamele edilen hücrelerde Bax ekspresyonunda artış ve Bcl-2 ekspresyonunda azalma gözlenmiştir. İmmünfloresan analizler apoptotik morfolojik değişiklikleri ortaya koymuştur. Bu bulgular, P. kurdica ekstraktlarının pankreas kanseri hücrelerinde antioksidan özelliklerin yanı sıra orta düzeyde sitotoksik ve anti-migratuvar etkiler gösterdiğini ve ileri farmakolojik araştırmalar için biyoaktif bileşik kaynağı olma potansiyeline sahip olduğunu desteklemektedir.

Keywords

• Paronychia kurdica
• fenolik bileşikler
• antioksidan aktivite
• pankreas kanseri
• apoptoz

In vitro antioxidant, cytotoxic, apoptotic, and anti-migratory effects of methanolic and aqueous extracts of Paronychia kurdica on pancreatic cancer cells

Abstract

Pancreatic cancer is one of the most lethal malignancies due to rapid metastasis and treatment resistance, with high post-diagnosis metastasis risk and low five-year survival rates. This study investigated the phenolic and flavonoid content, antioxidant capacity, and biological effects of Paronychia kurdica extracts on pancreatic cancer cells. The methanolic (MeOH) extract exhibited higher total phenolic (26.39 mg GAE/g) and flavonoid (21.52 mg QE/g) contents than the aqueous extract and demonstrated moderate antioxidant effect according to DPPH and FRAP assays. LC–MS analysis identified chlorogenic acid, rutin, ferulic acid, and p-coumaric acid in both extracts, with higher rutin levels in the MeOH extract. Both extracts showed dose-dependent cytotoxicity on MIA PaCa-2 cells (IC₅₀: MeOH 411.4 µg/mL, aqueous 385.5 µg/mL). Scratch assays indicated that the MeOH extract inhibited cell migration by 50.56–70.14%. Apoptotic mechanisms were confirmed by qRT-PCR and Western blot analyses, with increased Bax and decreased Bcl-2 expression, particularly in MeOH extract-treated cells. Immunofluorescence revealed apoptotic morphological changes. These findings suggest that P. kurdica extracts possess antioxidant properties along with moderate cytotoxic and anti-migratory effects in pancreatic cancer cells, supporting their potential as a source of bioactive compounds for further pharmacological investigation

Keywords

• Paronychia kurdica
• phenolic compounds
• antioxidant activity
• pancreatic cancer
• apoptosis

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