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Article

Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells

  • Authors:
    • Ling-Fei Wu
    • Bi-Liu Wei
    • Yi-Tian Guo
    • Yan-Qing Ye
    • Guo-Ping Li
    • Ze-Jin Pu
    • Jia-Lin Feng
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, P.R. China, Department of Information, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, P.R. China
  • Pages: 797-804
    |
    Published online on: August 2, 2012
       https://doi.org/10.3892/ijmm.2012.1085
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Abstract

Apoptosis plays a critical role in the development and homeostasis of multicellular organisms, and endoplasmic reticulum stress (ERS) is one of the intrinsic apoptosis pathways. Previous studies have shown that adenosine induces apoptosis in several cancer cell lines. However, the molecular mechanism remains poorly understood. In this study, we explored whether adenosine triggers apoptosis of EC109 esophageal carcinoma (EC) cells by ERS. The MTT assay was used to determine cell proliferation; cell cycle detection (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to determine cell apoptosis. The subcellular distribution and expression of the ERS-related proteins GRP78, cleaved caspase-3, cleaved caspase-4, CHOP and NF-κB p65 were detected by western blot techniques. NF-κB activation was measured by electrophoretic mobility shift assay (EMSA). The MTT assay demonstrated that adenosine inhibited EC109 cell proliferation in a dose- and time-dependent manner. FCM and TUNEL assay verified that adenosine caused an apoptotic peak in cell cycle arrest and a higher percentage of apoptotic cells. Western blot analysis confirmed that the expression of GRP78, cleaved caspase-4, CHOP, NF-κB p65 and cleaved caspase-3 were upregulated in a dose-dependent manner after adenosine treatment. EMSA revealed that adenosine activated NF-κB p65. This is the first demonstration that adenosine inhibits cell proliferation, increases GRP78 and NF-κB p65 expression and induces apoptosis by CHOP and caspase-4 pathways. The ERS pathway is involved in adenosine-induced apoptosis in EC109 cells.
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1. 

DM ParkinF BrayJ FerlayP PisaniGlobal cancer statistics, 2002CA Cancer J Clin5574108200510.3322/canjclin.55.2.74

2. 

RS HolmesTL VaughanEpidemiology and pathogenesis of esophageal cancerSemin Radiat Oncol1729200710.1016/j.semradonc.2006.09.00317185192

3. 

BB FredholmAdenosine, an endogenous distress signal, modulates tissue damage and repairCell Death Differ1413151323200710.1038/sj.cdd.440213217396131

4. 

CM GalmariniJR MackeyC DumontetNucleoside analogues and nucleobases in cancer treatmentLancet Oncol3415424200210.1016/S1470-2045(02)00788-X12142171

5. 

SP Seetulsingh-GoorahMechanisms of adenosine-induced cytotoxicity and their clinical and physiological implicationsBiofactors27213230200610.1002/biof.552027011917012777

6. 

W SunHE KhooCH TanAdenosine induced apoptosis in BHK cells via P1 receptors and equilibrative nucleoside transportersJ Biochem Mol Biol38314319200510.5483/BMBRep.2005.38.3.31415943907

7. 

LF WuGP LiJL FengZJ PuMolecular mechanisms of adenosine-induced apoptosis in human HepG2 cellsActa Pharmacol Sin27477484200610.1111/j.1745-7254.2006.00302.x16539849

8. 

S Casas-TintoY ZhangJ Sanchez-GarciaM Gomez-VelazquezDE Rincon-LimasP Fernandez-FunezThe ER stress factor XBP1s prevents amyloid-beta neurotoxicityHum Mol Genet2021442160201110.1093/hmg/ddr10021389082

9. 

YM ChoYS JangYM JangSM ChungHS KimJH LeeInduction of unfolded protein response during neuronal induction of rat bone marrow stromal cells and mouse embryonic stem cellsExp Mol Med41440452200910.3858/emm.2009.41.6.04919322020

10. 

H YoshidaT OkadaK HazeH YanagiT YuraM NegishiK MoriATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein responseMol Cell Biol2067556767200010.1128/MCB.20.18.6755-6767.200010958673

11. 

D DongC StapletonB LuoS XiongW YeY ZhangA critical role for GRP78/BiP in the tumor microenvironment for neovascularization during tumor growth and metastasisCancer Res7128482857201110.1158/0008-5472.CAN-10-315121467168

12. 

UK MisraS PayneSV PizzoLigation of prostate cancer cell surface GRP78 activates a proproliferative and antiapoptotic feedback loop: a role for secreted prostate-specific antigenJ Biol Chem28612481259201110.1074/jbc.M110.12976721056970

13. 

H ZinsznerM KurodaX WangN BatchvarovaRT LightfootH RemottiCHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulumGenes Dev12982995199810.1101/gad.12.7.9829531536

14. 

T NakagawaH ZhuN MorishimaE LiJ XuBA YanknerJ YuanCaspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-betaNature40398103200010.1038/4751310638761

15. 

F UranoX WangA BertolottiY ZhangP ChungHP HardingD RonCoupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1Science287664666200010.1126/science.287.5453.66410650002

16. 

L WuZ PuJ FengG LiZ ZhengW ShenThe ubiquitinproteasome pathway and enhanced activity of NF-kappaB in gastric carcinomaJ Surg Oncol97439444200810.1002/jso.2095218163448

17. 

AJ Robinson-WhiteHP HsiaoWW LeitnerE GreeneA BauerNL KrettProtein kinase A-independent inhibition of proliferation and induction of apoptosis in human thyroid cancer cells by 8-Cl-adenosineJ Clin Endocrinol Metab9310201029200810.1210/jc.2007-233118073299

18. 

E RapaportJ FontaineAnticancer activities of adenine nucleotides in mice are mediated through expansion of erythrocyte ATP poolsProc Natl Acad Sci USA8616621666198910.1073/pnas.86.5.16622922403

19. 

Y YasudaM SaitoT YamamuraT YaguchiT NishizakiExtracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A(2a) adenosine receptorsJ Gastroenterol445665200910.1007/s00535-008-2273-719159073

20. 

M HashemiF Karami-TehraniS GhavamiS MaddikaM LosAdenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathwayCell Prolif38269285200510.1111/j.1365-2184.2005.00349.x16202036

21. 

K GhiasC MaV GandhiLC PlataniasNL KrettST Rosen8-Amino-adenosine induces loss of phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt kinase: role in induction of apoptosis in multiple myelomaMol Cancer Ther4569577200510.1158/1535-7163.MCT-04-0303

22. 

Y ZhangR LiuM NiP GillAS LeeCell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiPJ Biol Chem2851506515075201010.1074/jbc.M109.08744520208072

23. 

UK MisraR DeedwaniaSV PizzoActivation and crosstalk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78J Biol Chem2811369413707200610.1074/jbc.M51169420016543232

24. 

J LiAS LeeStress induction of GRP78/BiP and its role in cancerCurr Mol Med64554200610.2174/15665240677557452316472112

25. 

AS LeeGRP78 induction in cancer: therapeutic and prognostic implicationsCancer Res6734963499200710.1158/0008-5472.CAN-07-032517440054

26. 

H ZhouY ZhangY FuL ChanAS LeeNovel mechanism of anti-apoptotic function of 78-kDa glucose-regulated protein (GRP78): endocrine resistance factor in breast cancer, through release of B-cell lymphoma 2 (BCL-2) from BCL-2-interacting killer (BIK)J Biol Chem2862568725696201110.1074/jbc.M110.212944

27. 

F RovettaA StacchiottiA ConsiglioM CadeiPG GrigolatoA LavazzaER signaling regulation drives the switch between autophagy and apoptosis in NRK-52E cells exposed to cisplatinExp Cell Res318238250201210.1016/j.yexcr.2011.11.008

28. 

HQ WangZX DuHY ZhangDX GaoDifferent induction of GRP78 and CHOP as a predictor of sensitivity to proteasome inhibitors in thyroid cancer cellsEndocrinology14832583270200710.1210/en.2006-156417431003

29. 

Z LiT ZhangH DaiG LiuH WangY SunEndoplasmic reticulum stress is involved in myocardial apoptosis of streptozocin-induced diabetic ratsJ Endocrinol196565572200810.1677/JOE-07-023018310452

30. 

C MazzoniC FalconeCaspase-dependent apoptosis in yeastBiochim Biophys Acta178313201327200818355456

31. 

J HitomiT KatayamaY EguchiT KudoM TaniguchiY KoyamaInvolvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell deathJ Cell Biol165347356200410.1083/jcb.20031001515123740

32. 

E PikarskyRM PoratI SteinR AbramovitchS AmitS KasemNF-kappaB functions as a tumour promoter in inflammation-associated cancerNature431461466200410.1038/nature0292415329734

33. 

J KucharczakMJ SimmonsY FanC GelinasTo be, or not to be: NF-kappaB is the answer - role of Rel/NF-kappaB in the regulation of apoptosisOncogene2289618982200310.1038/sj.onc.120723014663476

34. 

X DolcetD LlobetM EncinasJ PallaresA CaberoJA SchoenenbergerProteasome inhibitors induce death but activate NF-kappaB on endometrial carcinoma cell lines and primary culture explantsJ Biol Chem2812211822130200610.1074/jbc.M60135020016735506

35. 

I MeteogluIH ErdogduN MeydanM ErkusS BarutcaNF-kappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissuesJ Exp Clin Cancer Res2753200810.1186/1756-9966-27-5318928570

36. 

LF WuGP LiJD SuZJ PuJL FengYQ YeBL WeiInvolvement of NF-kappaB activation in the apoptosis induced by extracellular adenosine in human hepatocellular carcinoma HepG2 cellsBiochem Cell Biol88705714201020651843

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Copy and paste a formatted citation
Spandidos Publications style
Wu L, Wei B, Guo Y, Ye Y, Li G, Pu Z and Feng J: Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells. Int J Mol Med 30: 797-804, 2012.
APA
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., & Feng, J. (2012). Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells. International Journal of Molecular Medicine, 30, 797-804. https://doi.org/10.3892/ijmm.2012.1085
MLA
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., Feng, J."Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells". International Journal of Molecular Medicine 30.4 (2012): 797-804.
Chicago
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., Feng, J."Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells". International Journal of Molecular Medicine 30, no. 4 (2012): 797-804. https://doi.org/10.3892/ijmm.2012.1085
Copy and paste a formatted citation
x
Spandidos Publications style
Wu L, Wei B, Guo Y, Ye Y, Li G, Pu Z and Feng J: Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells. Int J Mol Med 30: 797-804, 2012.
APA
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., & Feng, J. (2012). Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells. International Journal of Molecular Medicine, 30, 797-804. https://doi.org/10.3892/ijmm.2012.1085
MLA
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., Feng, J."Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells". International Journal of Molecular Medicine 30.4 (2012): 797-804.
Chicago
Wu, L., Wei, B., Guo, Y., Ye, Y., Li, G., Pu, Z., Feng, J."Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 cells". International Journal of Molecular Medicine 30, no. 4 (2012): 797-804. https://doi.org/10.3892/ijmm.2012.1085
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