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The proteasome inhibition enhances apoptosis by P53 expression and the dissipation of mitochondrial transmembrane potential in TRAIL-resistant lung cancer cells  

Seol, Jae-Won (Center for Healthcare Technology Development, and Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Park, Sang-Youel (Center for Healthcare Technology Development, and Bio-safety Research Institute, College of Veterinary Medicine, Chonbuk National University)
Publication Information
Korean Journal of Veterinary Research / v.49, no.1, 2009 , pp. 1-8 More about this Journal
Abstract
The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.
Keywords
ALLN; caspases; MTP; P53; TRAIL;
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1 Brooks AD, Ramirez T, Toh U, Onksen J, Elliott PJ,Murphy WJ, Sayers TJ. The Proteasome InhibitorBortezomib (Velcade) Sensitizes Some Human TumorCells to Apo2L/TRAIL-Mediated Apoptosis. Ann N YAcad Sci 2005, 1059, 160-167   DOI   ScienceOn
2 Goldberg AL, Stein R, Adams J. New insights intoproteasome function: from archaebacteria to drugdevelopment. Chem Biol 1995, 2, 503-508   DOI   ScienceOn
3 Hammond EM, Giaccia AJ. The role of p53 inhypoxia-induced apoptosis. Biochem Biophys ResCommun 2005, 331, 718-725   DOI   ScienceOn
4 Inoue T, Shiraki K, Fuke H, Yamanaka Y, MiyashitaK, Yamaguchi Y, Yamamoto N, Ito K, Sugimoto K,Nakano T. Proteasome inhibition sensitizes hepatocellularcarcinoma cells to TRAIL by suppressingcaspase inhibitors and AKT pathway. Anticancer Drugs2006, 17, 261-268   DOI   ScienceOn
5 Ishizawa J, Yoshida S, Oya M, Mizuno R, ShinojimaT, Marumo K, Murai M. Inhibition of the ubiquitinproteasomepathway activates stress kinases andinduces apoptosis in renal cancer cells. Int J Oncol2004, 25, 697-702   PUBMED
6 Lim ML, Lum MG, Hansen TM, Roucou X, Nagley P. On the release of cytochrome c from mitochondriaduring cell death signaling. J Biomed Sci 2002, 9, 488-506   PUBMED
7 Mlynarczuk I, Hoser G, Grzela T, Stoklosa T,Wojcik C, Malejczyk J, Jakobisiak M. Augmentedpro-apoptotic effects of TRAIL and proteasomeinhibitor in human promonocytic leukemic U937 cells.Anticancer Res 2001, 21, 1237-1240   PUBMED
8 Nawrocki ST, Carew JS, Pino MS, Highshaw RA,Dunner K Jr, Huang P, Abbruzzese JL, McConkeyDJ. Bortezomib sensitizes pancreatic cancer cells toendoplasmic reticulum stress-mediated apoptosis. CancerRes 2005, 65, 11658-11666   DOI   ScienceOn
9 Pitti RM, Marsters SA, Ruppert S, Donahue CJ,Moore A, Ashkenazi A. Induction of apoptosis byApo-2 ligand, a new member of the tumor necrosisfactor cytokine family. J Biol Chem 1996, 271, 12687-12690   DOI   ScienceOn
10 Seol DW, Billiar TR. Cysteine 230 modulates tumornecrosis factor-related apoptosis-inducing ligand activity.Cancer Res 2000, 60, 3152-3154   PUBMED
11 Walczak H, Miller RE, Ariail K, Gliniak B, GriffithTS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT,Schuh JC, Lynch DH. Tumoricidal activity of tumornecrosis factor-related apoptosis-inducing ligand invivo. Nat Med 1999, 5, 157-163   DOI   ScienceOn
12 An WG, Hwang SG, Trepel JB, Blagosklonny MV.Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis areindependent markers of proteasome inhibition. Leukemia 2000, 14, 1276-1283   DOI   ScienceOn
13 Kim OH, Lim JH, Woo KJ, Kim YH, Jin IN, HanST, Park JW, Kwon TK. Influence of p53 andp21Waf1 expression on G2/M phase arrest of colorectalcarcinoma HCT116 cells to proteasome inhibitors. Int J Oncol 2004, 24, 935-941   PUBMED
14 Ling YH, Liebes L, Ng B, Buckley M, Elliott PJ,Adams J, Jiang JD, Muggia FM, Perez-Soler R. PS-341, a novel proteasome inhibitor, induces Bcl-2phosphorylation and cleavage in association with G2-M phase arrest and apoptosis. Mol Cancer Ther 2002,1, 841-849   PUBMED
15 Newmeyer DD, Ferguson-Miller S. Mitochondria:releasing power for life and unleashing the machineriesof death. Cell 2003, 112, 481-490   DOI   PUBMED   ScienceOn
16 He Q, Huang Y, Sheikh MS. Proteasome inhibitorMG132 upregulates death receptor 5 and cooperateswith Apo2L/TRAIL to induce apoptosis in Baxproficientand -deficient cells. Oncogene 2004, 23,2554-2558   DOI   ScienceOn
17 Coux O, Tanaka K, Goldberg AL. Structure andfunctions of the 20S and 26S proteasomes. Annu RevBiochem 1996, 65, 801-847   DOI   ScienceOn
18 Hansson LO, Friedler A, Freund S, Rudiger S,Fersht AR. Two sequence motifs from HIF-1alphabind to the DNA-binding site of p53. Proc Natl AcadSci USA 2002, 99, 10305-10309   DOI   ScienceOn
19 Lashinger LM, Zhu K, Williams SA, Shrader M,Dinney CP, McConkey DJ. Bortezomib abolishestumor necrosis factor-related apoptosis-inducing ligandresistance via a p21-dependent mechanism in humanbladder and prostate cancer cells. Cancer Res 2005, 65,4902-4908   DOI   ScienceOn
20 Kim K, Takimoto R, Dicker DT, Chen Y, Gazitt Y,El-Deiry WS. Enhanced TRAIL sensitivity by p53overexpression in human cancer but not normal celllines. Int J Oncol 2001, 18, 241-247   PUBMED
21 Chen JJ, Chou CW, Chang YF, Chen CC.Proteasome inhibitors enhance TRAIL-induced apoptosisthrough the intronic regulation of DR5: involvement of NF-kappa B and reactive oxygen species-mediated p53activation. J Immunol 2008, 180, 8030-8039   DOI
22 Cha SS, Kim MS, Choi YH, Sung BJ, Shin NK,Shin HC, Sung YC, Oh BH. 2.8 A resolution crystalstructure of human TRAIL, a cytokine with selectiveantitumor activity. Immunity 1999, 11, 253-261   DOI   ScienceOn
23 Hougardy BM, Maduro JH, van der Zee AG, deGroot DJ, van den Heuvel FA, de Vries EG, de JongS. Proteasome inhibitor MG132 sensitizes HPV-positivehuman cervical cancer cells to rhTRAIL-inducedapoptosis. Int J Cancer 2006, 118, 1892-1900   DOI   ScienceOn
24 Hymowitz SG, Christinger HW, Fuh G, Ultsch M,O'Connell M, Kelley RF, Ashkenazi A, de Vos AM.Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol Cell1999, 4, 563-571   DOI   ScienceOn
25 Yan XB, Yang DS, Gao X, Feng J, Shi ZL, Ye Z.Caspase-8 dependent osteosarcoma cell apoptosisinduced by proteasome inhibitor MG132. Cell Biol Int 2007, 31, 1136-1143   DOI   ScienceOn
26 Griffith TS, Anderson RD, Davidson BL, WilliamsRD, Ratliff TL. Adenoviral-mediated transfer of theTNF-related apoptosis-inducing ligand/Apo-2 ligandgene induces tumor cell apoptosis. J Immunol 2000,165, 2886-2894   DOI
27 Santer FR, Bacher N, Moser B, Morandell D,Ressler S, Firth SM, Spoden GA, Sergi C, Baxter RC, Jansen-Durr P, Zwerschke W. Nuclear insulinlikegrowth factor binding protein-3 induces apoptosisand is targeted to ubiquitin/proteasome-dependentproteolysis. Cancer Res 2006, 66, 3024-3033   DOI   ScienceOn
28 King RW, Deshaies RJ, Peters JM, Kirschner MW.How proteolysis drives the cell cycle. Science 1996,274, 1652-1659   DOI   PUBMED   ScienceOn
29 Kroemer G, Reed JC. Mitochondrial control of celldeath. Nat Med 2000, 6, 513-519   DOI   ScienceOn
30 Drexler HC. Activation of the cell death program byinhibition of proteasome function. Proc Natl Acad SciUSA 1997, 94, 855-860   DOI   ScienceOn
31 Voortman J, Resende TP, Abou El Hassan MA,Giaccone G, Kruyt FA. TRAIL therapy in non-smallcell lung cancer cells: sensitization to death receptormediatedapoptosis by proteasome inhibitor bortezomib.Mol Cancer Ther 2007, 6, 2103-2112   DOI   ScienceOn
32 Lu M, Dou QP, Kitson RP, Smith DM, GoldfarbRH. Differential effects of proteasome inhibitors on cellcycle and apoptotic pathways in human YT and Jurkatcells. J Cell Biochem 2006, 97, 122-134   DOI   ScienceOn
33 Wiley SR, Schooley K, Smolak PJ, Din WS, HuangCP, Nicholl JK, Sutherland GR, Smith TD, RauchC, Smith CA, Goodwin RG Identification andcharacterization of a new member of the TNF familythat induces apoptosis. Immunity 1995, 3, 673-682   DOI   ScienceOn
34 Wente MN, Eibl G, Reber HA, Friess H, Buchler MW, Hines OJ. The proteasome inhibitor MG132induces apoptosis in human pancreatic cancer cells.Oncol Rep 2005, 14, 1635-1638   PUBMED
35 Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORT1/FADDinteractingprotease, in Fas/APO-1- and TNF receptorinducedcell death. Cell 1996, 85, 803-815   DOI   ScienceOn
36 Ganten TM, Koschny R, Haas TL, Sykora J, Li-Weber M, Herzer K, Walczak H. Proteasomeinhibition sensitizes hepatocellular carcinoma cells, butnot human hepatocytes, to TRAIL. Hepatology 2005,42, 588-597   DOI   ScienceOn
37 Pagano M. Cell cycle regulation by the ubiquitinpathway. FASEB J 1997, 11, 1067-1075   DOI   PUBMED