Combined Effects of Protocatechuic Acid and 5-Fluorouracil on p53 Gene Expression and Apoptosis in Gastric Adenocarcinoma Cells

Objectives: This study evaluated the combined effects of protocatechuic acid (PCA) and 5-fluorouracil (5-FU) on gastric adenocarcinoma (AGS)cells.Materials and Methods: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry technique,real-time quantitative polymerase chain reaction, and Western blotting were used to investigate cytotoxic effects, colony formation, apoptosis, p53gene expression, and Bcl-2 protein level in AGS cells treated with 5-FU and PCA.Results: Our results demonstrated that PCA (500 µM) alone or in combination with 5-FU (10 µM) inhibited AGS cell proliferation, inhibited a colonyformation, and increased apoptosis compared with untreated control cells. Moreover, the combined 5-FU/PCA exposure led to upregulation of p53and downregulation of Bcl-2 protein when compared to the untreated control cells.Conclusion: The results demonstrate that the combined 5-FU/PCA may promote antiproliferative and pro-apoptotic effects with the inhibition ofcolony formation in AGS cells. The mechanisms by which the combined 5-FU/PCA exposure exerts its effects are associated with upregulation ofp53 gene expression and downregulation of Bcl-2 level. Therefore, the combination of 5-FU with PCA not only could be a promising approach topotentially reduce the dose requirements of 5-FU but also could promote apoptosis via p53 and Bcl-2 signaling pathways.Key words: Apoptosis, 5-fluorouracil, protocatechuic acid, gastric cancer, combination, colony formation

Gastrik Adenokarsinoma Hücrelerinde Protokateşuik Asit ve 5-Florourasilin p53 Gen Ekspresyonu ve Apoptoz Üzerine Kombine Etkileri

Amaç: Bu çalışma protokateşuik asit (PCA) ve 5-florourasilin (5-FU) gastrik adenokarsinoma (AGS) hücreleri üzerine kombine etkisini değerlendirmiştir. Gereç ve Yöntemler: 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromid yöntemi, koloni oluşturma yöntemi, akış sitometrisi tekniği, gerçek zamanlı kantitatif polimeraz zincir reaksiyonu ve Western blot yöntemleri 5-FU ve PCA’ya maruz kalan AGS hücrelerinde sitotoksisite, koloni oluşumu, apoptoz, p53 gen ekspresyonu ve Bcl-2 düzeylerini belirlemek için kullanılmıştır. Bulgular: Sonuçlarımız PCA’nın tek başına (500 µM) veya 5-FU (10 µM) ile kombinasyonunun uygulama yapılmamış kontrol hücrelerine göre AGS hücre proliferasyonunu ve koloni oluşturmunu inhibe ettiğini ve apoptozu artırdığını göstermiştir. Ek olarak, uygulama yapılmamış kontrol hücrelerine göre kombine 5-FU/PCA maruziyeti p53 düzeylerini artırmış ve Bcl-2 düzeylerini artırmıştır. Sonuç: Sonuçlar göstermiştir ki AGS hücrelerinde kombine 5-FU/PCA maruziyeti koloni oluşumunu inhibe ederek antiproliferatif ve pro-apoptotik etkiler başlatabilir. Kombine 5-FU/PCA maruziyetinin etki gösterme mekanizması p53 geninin artması ve Bcl-2 geninin azalması ile ilişkili olabilir.


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Turkish Journal of Pharmaceutical Sciences
  • ISSN: 1304-530X
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 2000


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