Combined Effects of Protocatechuic Acid and 5-Fluorouracil on p53 Gene Expression and Apoptosis in Gastric Adenocarcinoma Cells
Journal Title: Turkish Journal of Pharmaceutical Sciences - Year 2020, Vol 17, Issue 6
Abstract
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, p53 gene 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 colony formation, and increased apoptosis compared with untreated control cells. Moreover, the combined 5-FU/PCA exposure led to upregulation of p53 and 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 of colony formation in AGS cells. The mechanisms by which the combined 5-FU/PCA exposure exerts its effects are associated with upregulation of p53 gene expression and downregulation of Bcl-2 level. Therefore, the combination of 5-FU with PCA not only could be a promising approach to potentially reduce the dose requirements of 5-FU but also could promote apoptosis via p53 and Bcl-2 signaling pathways.
Authors and Affiliations
Zahra MOTAMEDI, Sayed Asadollah AMINI, Elham RAEISI, Yves LEMOIGNE, Esfandiar HEIDARIAN
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