Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells

Xia,Yuan; Zhang,Xulong; Bo,Agula; Sun,Juan; Li,Minhui

doi:10.3892/ol.2018.8111

Sodium citrate inhibits the proliferation of human gastric adenocarcinoma epithelia cells

Authors:
- Yuan Xia
- Xulong Zhang
- Agula Bo
- Juan Sun
- Minhui Li
View Affiliations

Affiliations: Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Inner Mongolia Autonomous Region 010021, P.R. China, Department of Immunology, College of Basic Medicine, Capital Medical University, Beijing 100069, P.R. China, School of Public Health, Inner Mongolia Medical University, Inner Mongolia Autonomous Region 010110, P.R. China, Department of National Medicine, Inner Mongolia Institute of Chinese Medicine, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China
Published online on: February 23, 2018 https://doi.org/10.3892/ol.2018.8111
Pages: 6622-6628

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The objective of the present study was to investigate the cytotoxic effects of sodium citrate on human gastric adenocarcinoma epithelia AGS cells. Numerous cytotoxicity‑associated sodium citrate‑induced effects were assessed, including cell viability and proliferation, cytokine expression and caspase activity. In vitro studies demonstrated that incubation with sodium citrate (>3.125 mM) inhibited AGS cell viability and proliferation in a dose‑dependent manner. Incubation with sodium citrate for 24 h revealed that the levels of interleukin‑1β (IL‑1β), IL‑8 and tumor necrosis factor increased with an increasing of dose of sodium citrate, whereas the IL‑6 levels exhibited only a slight alteration. In addition, increases in caspase‑3 and ‑9 activities were associated with increased duration of treatment and dosage of sodium citrate. Collectively, the results of the present study demonstrated that treatment with sodium citrate at higher concentrations or for longer durations exerts a cytotoxic effect on AGS cells via the induction of the intrinsic apoptosis pathway and the alteration in the levels of certain cytokines.

View Figures

View References

1	Leumann E, Hoppe B, Neuhaus T and Blau N: Efficacy of oral citrate administration in primary hyperoxaluria. Nephrol Dial Transpl. 10 Suppl 8:S14–S16. 1995. View Article : Google Scholar
2	Phillips R, Hanchanale VS, Myatt A, Somani B, Nabi G and Biyani CS: Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev: CD010057. 2015. View Article : Google Scholar
3	Pastorino J, Hansen CL and McMahon DJ: Effect of sodium citrate on structure-function relationships of Cheddar cheese. J Dairy Sci. 86:3113–3121. 2003. View Article : Google Scholar : PubMed/NCBI
4	Westergaard N, Waagepetersen HS, Belhage B and Schousboe A: Citrate, a ubiquitous key metabolite with regulatory function in the CNS. Neurochem Res. 42:1583–1588. 2017. View Article : Google Scholar : PubMed/NCBI
5	Wang JY, Zhu SG and Xu CF: Essential Biochemistry. 1st. 20. Higher Education Press; Beijing: pp. 340–342. 2010
6	Warburg O, Wind F and Negelein E: The metabolism of tumors in the body. J Gen Physiol. 8:519–530. 1927. View Article : Google Scholar : PubMed/NCBI
7	Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI
8	Moreno-Sánchez R, Rodríguez-Enríquez S, Marín-Hernández A and Saavedra E: Energy metabolism in tumor cells. FEBS J. 274:1393–1418. 2007. View Article : Google Scholar : PubMed/NCBI
9	Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhang X, Varin E, Allouche S, Lu Y, Poulain L and Icard P: Effect of citrate on malignant pleural mesothelioma cells: A synergistic effect with cisplatin. Anticancer Res. 29:1249–1254. 2009.PubMed/NCBI
11	Izyumov DS, Avetisyan AV, Pletjushkina OY, Sakharov DV, Wirtz KW, Chernyak BV and Skulachev VP: ‘Wages of fear’: Transient threefold decrease in intracellular ATP level imposes apoptosis. Biochim Biophys Acta. 1658:141–147. 2004. View Article : Google Scholar : PubMed/NCBI
12	Vander Heiden MG, Chandel NS, Schumacker PT and Thompson CB: Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. Mol Cell. 3:159–167. 1999. View Article : Google Scholar : PubMed/NCBI
13	Yousefi S, Owens JW and Cesario TC: Citrate shows specific, dose-dependent lympholytic activity in neoplastic cell lines. Leuk Lymphoma. 45:1657–1665. 2004. View Article : Google Scholar : PubMed/NCBI
14	Wang YS and Wang ZY: Sodium citrate induces apoptosis in biocontrol yeast Cryptococcus laurentii. J Appl Microbiol. 113:135–142. 2012. View Article : Google Scholar : PubMed/NCBI
15	Sun J, Misumi A, Shimaoka K, Aoki F and Esaki F: Stomach cancer-related mortality. Eur J Cancer Prev. 10:61–67. 2001. View Article : Google Scholar : PubMed/NCBI
16	Hamashima C: Current issues and future perspectives of gastric cancer screening. World J Gastroenterol. 20:13767–13774. 2014. View Article : Google Scholar : PubMed/NCBI
17	Wang XQ, Terry PD and Yan H: Review of salt consumption and stomach cancer risk: Epidemiological and biological evidence. World J Gastroenterol. 15:2204–2213. 2009. View Article : Google Scholar : PubMed/NCBI
18	Reeves GK, Pirie K, Green J, Bull D and Beral V; Million Women Study Collaborators, : Comparison of the effects of genetic and environmental risk factors on in situ and invasive ductal breast cancer. Int J Cancer. 131:930–937. 2012. View Article : Google Scholar : PubMed/NCBI
19	Sun J, Bi L, Chi Y, Aoki K and Misumi J: Effect of sodium acetate on cell proliferation and induction of proinflammatory cytokines: A preliminary evaluation. Food Chem Toxicol. 43:1773–1780. 2005. View Article : Google Scholar : PubMed/NCBI
20	Sun J, Aoki K, Wang W, Guo A and Misumi J: Sodium nitrite-induced cytotoxicity in cultured human gastric epithelial cells. Toxicol in Vitro. 20:1133–1138. 2006. View Article : Google Scholar : PubMed/NCBI
21	Zhang X, Bo A, Chi B, Xia Y, Su X and Sun J: Magnesium sulfate induced toxicity in vitro in AGS gastric adenocarcinoma cells and in vivo in mouse gastric mucosa. Asian Pac J Cancer Prev. 16:71–76. 2015. View Article : Google Scholar : PubMed/NCBI
22	Lu Y, Zhang X, Zhang H, Lan J, Huang G, Varin E, Lincet H, Poulain L and Icard P: Citrate induces apoptotic cell death: A promising way to treat gastric carcinoma? Anticancer Res. 31:797–805. 2011.PubMed/NCBI
23	Guo X, Zhang X, Wang T, Xian S and Lu Y: 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway. Biochem Biophys Res Commun. 475:37–43. 2016. View Article : Google Scholar : PubMed/NCBI
24	Barranco SC, Townsend CM Jr, Casartelli JC, Macik BG, Burger NL, Boerwinkle WR and Gourley WK: Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. Cancer Res. 43:1703–1709. 1983.PubMed/NCBI
25	Xintaropoulou C, Ward C, Wise A, Marston H, Turnbull A and Langdon SP: A comparative analysis of inhibitors of the glycolysis pathway in breast and ovarian cancer cell line models. Oncotarget. 6:25677–25695. 2015. View Article : Google Scholar : PubMed/NCBI
26	Randle PJ, Denton RM and England PJ: Citrate as a metabolic regulator in muscle and adipose tissue. Biochem Soc Symp. 27:87–103. 1968.PubMed/NCBI
27	Icard P, Poulain L and Lincet H: Understanding the central role of citrate in the metabolism of cancer cells. Biochim Biophys Acta. 1825:111–116. 2012.PubMed/NCBI
28	Elinos-Báez CM, Maldonado V and Meléndezzajgla J: Caspases: Apoptosis inducing molecules. Gac Med Mex. 139:493–499. 2003.(In Spanish). PubMed/NCBI
29	Riedl SJ and Shi Y: Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol. 5:897–907. 2004. View Article : Google Scholar : PubMed/NCBI
30	Kruspig B, Nilchian A, Orrenius S, Zhivotovsky B and Gogvadze V: Citrate kills tumor cells through activation of apical caspases. Cell Mol Life Sci. 69:4229–4237. 2012. View Article : Google Scholar : PubMed/NCBI
31	Kim GY, Park SY, Jo A, Kim M, Leem SH, Jun WJ, Shim SI, Lee SC and Chung JW: Gecko proteins induce the apoptosis of bladder cancer 5637 cell by inhibiting Akt and activating intrinsic caspase cascade. BMB Rep. 48:531–536. 2015. View Article : Google Scholar : PubMed/NCBI
32	Creagh EM: Caspase crosstalk: Integration of apoptotic and innate immune signalling pathways. Trends Immunol. 35:631–640. 2014. View Article : Google Scholar : PubMed/NCBI
33	Persson C, Canedo P, Machado JC, El-Omar EM and Forman D: Polymorphisms in inflammatory response genes and their association with gastric cancer: A HuGE systematic review and meta-analyses. Am J Epidemiol. 173:259–270. 2011. View Article : Google Scholar : PubMed/NCBI