Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence

Zhang,Zhun; Song,Ning; Peng,Yanping; Fan,Ziyan; Han,Mingyong; Zhao,Min; Dong,Tianyi; Liu,Shili

doi:10.3892/or.2018.6856

Evironmental pollutant perfluorodecanoic acid upregulates cIAP2 to suppress gastric cell senescence

Authors:
- Zhun Zhang
- Ning Song
- Yanping Peng
- Ziyan Fan
- Mingyong Han
- Min Zhao
- Tianyi Dong
- Shili Liu
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Affiliations: Department of Medical Microbiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China, China National Tobacco Quality Supervision and Test Center, Zhengzhou, Henan 450001, P.R. China, Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China, Department of Clinical Laboratory, Qilu Hospital of Shandong University, Qingdao, Shandong 266035, P.R. China
Published online on: November 9, 2018 https://doi.org/10.3892/or.2018.6856
Pages: 981-988

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Abstract

The role of perfluorodecanoic acid (PFDA) in gastric carcinogenesis and its mechanism remains unknown. Our previous research revealed that PFDA regulated the growth of human gastric cells. However, its core molecules and basic mechanisms are still not clear. In the present study, cDNA microarrays were used to determine mRNA changes in AGS cells after treatment with PFDA. DAVID analysis of the genes with >2‑fold increased expression in microarray data revealed five genes which were involved in cancer pathways. The most upregulated gene was cIAP2, whose upregulation in AGS was confirmed by western blot analysis and quantitative PCR (qPCR) analyses. In order to investigate the role of cIAP2 in cell proliferation, cIAP2 siRNA was employed to regulate cIAP2 expression following PFDA treatment. The results revealed that the growth rate of cIAP2‑knockdown cells was reduced by about 50% compared to the control. Given that our previous flow cytometric assays revealed no significant change (3.7 vs. 6.4%) in the percentage of apoptotic cells when PFDA was added to the medium and cIAP2 expression was upregulated, we next applied flow cytometry to assess whether cIAP2 would lead to cell cycle variations. The research data revealed that the proportion of cells in the G1, S and G2 phases was not significantly altered with the decrease of cIAP2 expression. Finally, the role of cIAP2 in AGS cell senescence was investigated, and the results indicated that cell senescence was significantly increased in the cIAP2 siRNA group in comparison to the control siRNA group. Since p53 has been identified as a tumor suppressor and its molecular alterations are common in different human tumors, we investigated the relationship of p53 with cIAP2. The experimental results demonstrated that cIAP2 regulated the expression of p53 and thus was likely to be a potential mechanism for PFDA‑induced growth promotion. Overall, the results revealed that PFDA may suppress cellular senescence induced by p53 through the regulation of cIAP2 protein expression.

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1	Ashley DJ: Environmental factors in the aetiology of gastric cancer. Br J Prev Soc Med. 23:187–189. 1969.PubMed/NCBI
2	Winkelstein WJ and Kantor S: Stomach cancer. Positive association with suspended particulate air pollution. Arch Environ Health. 18:544–547. 1969. View Article : Google Scholar : PubMed/NCBI
3	Zou X: Environmental pollution and epidemic of common cancers in China. Ke Ji Dao Bao. 32:58–64. 2014.
4	Guenthner R and Vietork L: Surface active materials from perfluorocarboxylic and perfluorosulfonilic acids. I&ED Prod Res Dev. 1:165–169. 1962. View Article : Google Scholar
5	Shinoda K and Nomura T: Miscibility of fluorocarbon and hydrocarbon surfactant in micelles and liquid mixtures: Basic studies of oil repellent and fire extinguishing agents. J Phys Chem. 8:365–369. 1980. View Article : Google Scholar
6	Mak YL, Taniyasu S, Yeung LW, Lu G, Jin L, Yang Y, Lam PK, Kannan K and Yamashita N: Perfluorinated compounds in tap water from China and several other countries. Environ Sci Technol. 43:4824–4829. 2009. View Article : Google Scholar : PubMed/NCBI
7	Wang JM, YY P, YL S and YQ C: Perfluorinated compounds pollution levels in snowfall of Beijing urban area. Scientia Sinica Chimica. 41:900–906. 2011. View Article : Google Scholar
8	Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Tully JS and Needham LL: Serum concentrations of 11 polyfluoroalkyl compounds in the u.s. population: Data from the national health and nutrition examination survey (NHANES). Environ Sci Technol. 41:2237–2242. 2007. View Article : Google Scholar : PubMed/NCBI
9	Calafat AM, Wong LY, Kuklenyik Z, Reidy JA and Needham LL: Polyfluoroalkyl chemicals in the U.S. population: Data from the national health and nutrition examination survey (NHANES) 2003–2004 and comparisons with NHANES 1999–2000. Environ Health Perspect. 115:1596–1602. 2007. View Article : Google Scholar : PubMed/NCBI
10	Fei C, McLaughlin JK, Tarone RE and Olsen J: Fetal growth indicators and perfluorinated chemicals: A study in the Danish national birth cohort. Am J Epidemiol. 168:66–72. 2008. View Article : Google Scholar : PubMed/NCBI
11	Nguyen VT, Gin KY, Reinhard M and Liu C: Occurrence, fate, and fluxes of perfluorochemicals (PFCs) in an urban catchment: Marina reservoir, Singapore. Water Sci Technol. 66:2439–2446. 2012. View Article : Google Scholar : PubMed/NCBI
12	Olsen GW, Church TR, Larson EB, van Belle G, Lundberg JK, Hansen KJ, Burris JM, Mandel JH and Zobel LR: Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an elderly population from Seattle, Washington. Chemosphere. 54:1599–1611. 2004. View Article : Google Scholar : PubMed/NCBI
13	Tao L, Kannan K, Aldous KM, Mauer MP and Eadon GA: Biomonitoring of perfluorochemicals in plasma of New York State personnel responding to the World trade center disaster. Environ Sci Technol. 42:3472–3478. 2008. View Article : Google Scholar : PubMed/NCBI
14	Oono S, Matsubara E, Harada KH, Takagi S, Hamada S, Asakawa A, Inoue K, Watanabe I and Koizumi A: Survey of airborne polyfluorinated telomers in Keihan area, Japan. Bull Environ Contam Toxicol. 80:102–106. 2008. View Article : Google Scholar : PubMed/NCBI
15	Skutlarek D, Exner M and Färber H: Perfluorinated surfactants in surface and drinking waters. Environ Sci Pollut Res Int. 13:299–307. 2006. View Article : Google Scholar : PubMed/NCBI
16	George ME and Andersen ME: Toxic effects of nonadecafluoro-n-decanoic acid in rats. Toxicol Appl Pharmacol. 85:169–180. 1986. View Article : Google Scholar : PubMed/NCBI
17	Harris MW, Uraih LC and Birnbaum LS: Acute toxicity of perfluorodecanoic acid in C57BL/6 mice differs from 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fundam Appl Toxicol. 13:723–736. 1989. View Article : Google Scholar : PubMed/NCBI
18	Chinje E, Kentish P, Jarnot B, George M and Gibson G: Induction of CYP4A subfamily by perfluorodecanoic acid: The rat and guinea pig as susceptible and non-susceptible species. Toxicol Lett. 71:69–75. 1994. View Article : Google Scholar : PubMed/NCBI
19	Kawashima Y, Kobayashi H, Miura H and Kozuka H: Characterization of hepatic response of rat to administration of perfluorooctanoic acid and perfluorodecanoic acid at low levels. Toxicology. 99:169–178. 1995. View Article : Google Scholar : PubMed/NCBI
20	Reo NV, Narayanan L, Kling KB and Adinehzadeh M: Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP: Phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver. Toxicol Lett. 86:1–11. 1996. View Article : Google Scholar : PubMed/NCBI
21	Sterchele PF, Vanden Heuvel JP, Davis JW II, Shrago E, Knudsen J and Peterson RE: Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels. Biochem Pharmacol. 48:955–966. 1994. View Article : Google Scholar : PubMed/NCBI
22	Vanden Heuvel JP: Perfluorodecanoic acid as a useful pharmacologic tool for the study of peroxisome proliferation. Gen Pharmac. 27:1123–1129. 1996. View Article : Google Scholar
23	Olson CT and Andersen ME: The acute toxicity of perfluorooctanoic and perfluorodecanoic acids in male rats and effects on tissue fatty acids. Toxicol Appl Pharmacol. 70:362–372. 1983. View Article : Google Scholar : PubMed/NCBI
24	Langley AE: Effects of perfluoro-n-decanoic acid on the respiratory activity of isolated rat liver mitochondria. J Toxicol Environ Health. 29:329–336. 1990. View Article : Google Scholar : PubMed/NCBI
25	Benninghoff AD, Bisson WH, Koch DC, Ehresman DJ, Kolluri SK and Williams DE: Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro. Toxicol Sci. 120:42–58. 2011. View Article : Google Scholar : PubMed/NCBI
26	Bookstaff RC, Moore RW, Ingall GB and Peterson RE: Androgenic deficiency in male rats treated with perfluorodecanoic acid. Toxicol Appl Pharmacol. 104:322–333. 1990. View Article : Google Scholar : PubMed/NCBI
27	Gutshall DM, Pilcher GD and Langley AE: Mechanism of the serum thyroid hormone lowering effect of perfluoro-n-decanoic acid (PFDA) in rats. J Toxicol Environ Health. 28:53–65. 1989. View Article : Google Scholar : PubMed/NCBI
28	Van Rafelghem MJ, Inhorn SL and Peterson RE: Effects of perfluorodecanoic acid on thyroid status in rats. Toxicol Appl Pharmacol. 87:430–439. 1987. View Article : Google Scholar : PubMed/NCBI
29	Borges T, Peterson RE, Pitot HC, Robertson LW and Glauert HP: Effect of the peroxisome proliferator perfluorodecanoic acid on the promotion of two-stage hepatocarcinogenesis in rats. Cancer Lett. 72:111–120. 1993. View Article : Google Scholar : PubMed/NCBI
30	Upham BL, Deocampo ND, Wurl B and Trosko JE: Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail. Int J Cancer. 78:491–495. 1998. View Article : Google Scholar : PubMed/NCBI
31	Nelson DL, Frazier DE Jr, Ericson JE, Tarr MJ and Mathes LE: The effects of perfluorodecanoic acid (PFDA) on humoral, cellular, and innate immunity in Fischer 344 rats. Immunopharmacol Immunotoxicol. 14:925–938. 1992. View Article : Google Scholar : PubMed/NCBI
32	Klenow S, Heinemeyer G, Brambilla G, Dellatte E, Herzke D and de Voogt P: Dietary exposure to selected perfluoroalkyl acids (PFAAs) in four European regions. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 30:2141–2151. 2013. View Article : Google Scholar : PubMed/NCBI
33	Dong T, Peng Y, Zhong N, Liu F, Zhang H, Xu M, Liu R, Han M, Tian X, Jia J, et al: Perfluorodecanoic acid (PFDA) promotes gastric cell proliferation via sPLA2-IIA. Oncotarget. 8:50911–50920. 2017.PubMed/NCBI
34	Deitch AD, Law H and deVere White R: A stable propidium iodide staining procedure for flow cytometry. J Histochem Cytochem. 30:967–972. 1982. View Article : Google Scholar : PubMed/NCBI
35	Cristofalo VJ: SA-beta-Gal staining: Biomarker or delusion. Exp Gerontol. 40:836–838. 2005. View Article : Google Scholar : PubMed/NCBI
36	Kurz DJ, Decary S, Hong Y and Erusalimsky JD: Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells. J Cell Sci. 113:3613–3622. 2000.PubMed/NCBI
37	Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI
38	Woodburn JR: The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol Ther. 82:241–250. 1999. View Article : Google Scholar : PubMed/NCBI
39	Gyrd-Hansen M and Meier P: IAPs: From caspase inhibitors to modulators of NF-kappaB, inflammation and cancer. Nat Rev Cancer. 10:561–574. 2010. View Article : Google Scholar : PubMed/NCBI
40	Pedersen J, LaCasse EC, Seidelin JB, Coskun M and Nielsen OH: Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation. Trends Mol Med. 20:652–665. 2014. View Article : Google Scholar : PubMed/NCBI
41	Dai Z, Zhu WG, Morrison CD, Brena RM, Smiraglia DJ, Raval A, Wu YZ, Rush LJ, Ross P, Molina JR, et al: A comprehensive search for DNA amplification in lung cancer identifies inhibitors of apoptosis cIAP1 and cIAP2 as candidate oncogenes. Hum Mol Genet. 12:791–801. 2003. View Article : Google Scholar : PubMed/NCBI
42	Reardon DA, Michalkiewicz E, Boyett JM, Sublett JE, Entrekin RE, Ragsdale ST, Valentine MB, Behm FG, Li H, Heideman RL, et al: Extensive genomic abnormalities in childhood medulloblastoma by comparative genomic hybridization. Cancer Res. 57:4042–4047. 1997.PubMed/NCBI
43	Vermeulen K, Van Bockstaele DR and Berneman ZN: The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36:131–149. 2003. View Article : Google Scholar : PubMed/NCBI
44	Jin HS and Lee TH: Cell cycle-dependent expression of cIAP2 at G2/M phase contributes to survival during mitotic cell cycle arrest. Biochem J. 399:335–342. 2006. View Article : Google Scholar : PubMed/NCBI
45	Hayflick L and Moorhead PS: The serial cultivation of human diploid cell strains. Exp Cell Res. 25:585–621. 1961. View Article : Google Scholar : PubMed/NCBI
46	Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 37:614–636. 1965. View Article : Google Scholar : PubMed/NCBI
47	Brown JP, Wei W and Sedivy JM: Bypass of senescence after disruption of p21^CIP1/WAF1 gene in normal diploid human fibroblasts. Science. 277:831–834. 1997. View Article : Google Scholar : PubMed/NCBI
48	Xu HJ, Zhou Y, Ji W, Perng GS, Kruzelock R, Kong CT, Bast RC, Mills GB, Li J and Hu SX: Reexpression of the retinoblastoma protein in tumor cells induces senescence and telomerase inhibition. Oncogene. 15:2589–2596. 1997. View Article : Google Scholar : PubMed/NCBI
49	Rogan EM, Bryan TM, Hukku B, Maclean K, Chang AC, Moy EL, Englezou A, Warneford SG, Dalla-Pozza L and Reddel RR: Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol Cell Biol. 15:4745–4753. 1995. View Article : Google Scholar : PubMed/NCBI
50	Whitaker NJ, Bryan TM, Bonnefin P, Chang AC, Musgrove EA, Braithwaite AW and Reddel RR: Involvement of RB-1, p53, p16INK4 and telomerase in immortalisation of human cells. Oncogene. 11:971–976. 1995.PubMed/NCBI
51	Capparelli C, Chiavarina B, Whitaker-Menezes D, Pestell TG, Pestell RG, Hulit J, Andò S, Howell A, Martinez-Outschoorn UE, Sotgia F, et al: CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, ‘fueling’ tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle. 11:3599–3610. 2012. View Article : Google Scholar : PubMed/NCBI
52	Lin AW, Barradas M, Stone JC, van Aelst L, Serrano M and Lowe SW: Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev. 12:3008–3019. 1998. View Article : Google Scholar : PubMed/NCBI
53	Helman A, Klochendler A, Azazmeh N, Gabai Y, Horwitz E, Anzi S, Swisa A, Condiotti R, Granit RZ, Nevo Y, et al: p16^Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion. Nat Med. 22:412–420. 2016. View Article : Google Scholar : PubMed/NCBI
54	Marcoux S, Le ON, Langlois-Pelletier C, Laverdière C, Hatami A, Robaey P and Beauséjour CM: Expression of the senescence marker p16^INK4a in skin biopsies of acute lymphoblastic leukemia survivors: A pilot study. Radiat Oncol. 8:2522013. View Article : Google Scholar : PubMed/NCBI
55	Zhou X, Dong T, Fan Z, Peng Y, Zhou R, Wang X, Song N, Han M, Fan B, Jia J and Liu S: Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells. Sci Rep. 7:454682017. View Article : Google Scholar : PubMed/NCBI