Zahra Motamedi1, Sayed Asadollah Amini2, Elham Raeisi3, Yves Lemoigne4, Esfandiar Heidarian1. 1. Shahrekord University of Medical Sciences, Basic Health Sciences Institute, Clinical Biochemistry Research Center, Shahrekord, Iran. 2. Shahrekord University of Medical Sciences, Basic Health Sciences Institute, Cellular and Molecular Research Center, Shahrekord, Iran. 3. Shahrekord University of Medical Sciences, Department of Medical Physics and Radiology, School of Allied Medical Sciences, Shahrekord, Iran. 4. Institute for Medical Physics, Ambilly, France.
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.
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: Boyu Pan; Yafei Xia; Zilu Gao; Gang Zhao; Liangjiao Wang; Senbiao Fang; Liren Liu; Shu Yan Journal: Chin Med Date: 2022-03-09 Impact factor: 5.455