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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism

Authors: Konstantin Golovine, Peter Makhov, Robert G Uzzo, Alexander Kutikov, David J Kaplan, Eric Fox, Vladimir M Kolenko

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Cadmium has been classified as a human carcinogen, affecting health through occupational and environmental exposure. Cadmium has a long biological half-life (>25 years), due to the flat kinetics of its excretion. The prostate is one of the organs with highest levels of cadmium accumulation. Importantly, patients with prostate cancer appear to have higher levels of cadmium both in the circulation and in prostatic tissues.

Results

In the current report, we demonstrate for the first time that cadmium down-regulates expression of the X-linked inhibitor of apoptosis protein (XIAP) in prostate cancer cells. Cadmium-mediated XIAP depletion occurs at the post-transcriptional level via an NF-κB-independent, proteasome-mediated mechanism and coincides with an increased sensitivity of prostate cancer cells to TNF-α-mediated apoptosis. Prolonged treatment with cadmium results in selection of prostate cancer cells with apoptosis-resistant phenotype. Development of apoptosis-resistance coincides with restoration of XIAP expression in cadmium-selected PC-3 cells.

Conclusions

Selection of cadmium-resistant cells could represent an adaptive survival mechanism that may contribute to progression of prostatic malignancies.
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Literature
1.
2.
Krone CA, Wyse EJ, Ely JT: Cadmium in zinc-containing mineral supplements. Int J Food Sci Nutr. 2001, 52: 379-382. 10.1080/09637480120057602CrossRefPubMed
3.
Kim BJ, Kim MS, Kim KB, Kim KW, Hong YM, Kim IK, Lee HW, Jung YK: Sensitizing effects of cadmium on TNF-alpha- and TRAIL-mediated apoptosis of NIH3T3 cells with distinct expression patterns of p53. Carcinogenesis. 2002, 23: 1411-1417. 10.1093/carcin/23.9.1411CrossRefPubMed
4.
Achanzar WE, Achanzar KB, Lewis JG, Webber MM, Waalkes MP: Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis. Toxicol Appl Pharmacol. 2000, 164: 291-300. 10.1006/taap.1999.8907CrossRefPubMed
5.
Bakshi S, Zhang X, Godoy-Tundidor S, Cheng RY, Sartor MA, Medvedovic M, Ho SM: Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor. Environ Health Perspect. 2008, 116: 769-776. 10.1289/ehp.11215PubMedCentralCrossRefPubMed
6.
Nakamura K, Yasunaga Y, Ko D, Xu LL, Moul JW, Peehl DM, Srivastava S, Rhim JS: Cadmium-induced neoplastic transformation of human prostate epithelial cells. Int J Oncol. 2002, 20: 543-547.PubMed
7.
Waalkes MP, Rehm S, Cherian MG: Repeated cadmium exposures enhance the malignant progression of ensuing tumors in rats. Toxicol Sci. 2000, 54: 110-120. 10.1093/toxsci/54.1.110CrossRefPubMed
8.
Waalkes MP, Rehm S, Perantoni AO, Coogan TP: Cadmium exposure in rats and tumours of the prostate. IARC Sci Publ. 1992, 391-400.
9.
Martin JJ, Martin R, Codesal J, Fraile B, Paniagua R, Santamaria L: Cadmium chloride-induced dysplastic changes in the ventral rat prostate: an immunohistochemical and quantitative study. Prostate. 2001, 46: 11-20. 10.1002/1097-0045(200101)46:1<11::AID-PROS1003>3.0.CO;2-KCrossRefPubMed
10.
Brys M, Nawrocka AD, Miekos E, Zydek C, Foksinski M, Barecki A, Krajewska WM: Zinc and cadmium analysis in human prostate neoplasms. Biol Trace Elem Res. 1997, 59: 145-152. 10.1007/BF02783239CrossRefPubMed
11.
Goyer RA, Liu J, Waalkes MP: Cadmium and cancer of prostate and testis. Biometals. 2004, 17: 555-558. 10.1023/B:BIOM.0000045738.59708.20CrossRefPubMed
12.
Deveraux QL, Takahashi R, Salvesen GS, Reed JC: X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 1997, 388: 300-304. 10.1038/40901CrossRefPubMed
13.
Eckelman BP, Salvesen GS, Scott FL: Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep. 2006, 7: 988-994. 10.1038/sj.embor.7400795PubMedCentralCrossRefPubMed
14.
Hofer-Warbinek R, Schmid JA, Stehlik C, Binder BR, Lipp J, de Martin R: Activation of NF-kappa B by XIAP, the X chromosome-linked inhibitor of apoptosis, in endothelial cells involves TAK1. J Biol Chem. 2000, 275: 22064-22068. 10.1074/jbc.M910346199CrossRefPubMed
15.
Uren AG, Beilharz T, O'Connell MJ, Bugg SJ, van Driel R, Vaux DL, Lithgow T: Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division. Proc Natl Acad Sci USA. 1999, 96: 10170-10175. 10.1073/pnas.96.18.10170PubMedCentralCrossRefPubMed
16.
Yang Y, Fang S, Jensen JP, Weissman AM, Ashwell JD: Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science. 2000, 288: 874-877. 10.1126/science.288.5467.874CrossRefPubMed
17.
Schimmer AD, Dalili S, Batey RA, Riedl SJ: Targeting XIAP for the treatment of malignancy. Cell Death Differ. 2006, 13: 179-188. 10.1038/sj.cdd.4401826CrossRefPubMed
18.
Kashkar H, Deggerich A, Seeger JM, Yazdanpanah B, Wiegmann K, Haubert D, Pongratz C, Kronke M: NF-kappaB-independent down-regulation of XIAP by bortezomib sensitizes HL B cells against cytotoxic drugs. Blood. 2007, 109: 3982-3988. 10.1182/blood-2006-10-053959CrossRefPubMed
19.
Krajewska M, Kim H, Kim C, Kang H, Welsh K, Matsuzawa S, Tsukamoto M, Thomas RG, Assa-Munt N, Piao Z: Analysis of apoptosis protein expression in early-stage colorectal cancer suggests opportunities for new prognostic biomarkers. Clin Cancer Res. 2005, 11: 5451-5461. 10.1158/1078-0432.CCR-05-0094CrossRefPubMed
20.
Hofmann HS, Simm A, Hammer A, Silber RE, Bartling B: Expression of inhibitors of apoptosis (IAP) proteins in non-small cell human lung cancer. J Cancer Res Clin Oncol. 2002, 128: 554-560. 10.1007/s00432-002-0364-zCrossRefPubMed
21.
Mizutani Y, Nakanishi H, Li YN, Matsubara H, Yamamoto K, Sato N, Shiraishi T, Nakamura T, Mikami K, Okihara K: Overexpression of XIAP expression in renal cell carcinoma predicts a worse prognosis. Int J Oncol. 2007, 30: 919-925.PubMed
22.
Shiraki K, Sugimoto K, Yamanaka Y, Yamaguchi Y, Saitou Y, Ito K, Yamamoto N, Yamanaka T, Fujikawa K, Murata K, Nakano T: Overexpression of X-linked inhibitor of apoptosis in human hepatocellular carcinoma. Int J Mol Med. 2003, 12: 705-708.PubMed
23.
Berezovskaya O, Schimmer AD, Glinskii AB, Pinilla C, Hoffman RM, Reed JC, Glinsky GV: Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res. 2005, 65: 2378-2386. 10.1158/0008-5472.CAN-04-2649CrossRefPubMed
24.
Nomura T, Yamasaki M, Nomura Y, Mimata H: Expression of the inhibitors of apoptosis proteins in cisplatin-resistant prostate cancer cells. Oncol Rep. 2005, 14: 993-997.PubMed
25.
Cao C, Mu Y, Hallahan DE, Lu B: XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer. Oncogene. 2004, 23: 7047-7052. 10.1038/sj.onc.1207929CrossRefPubMed
26.
Meplan C, Mann K, Hainaut P: Cadmium induces conformational modifications of wild-type p53 and suppresses p53 response to DNA damage in cultured cells. J Biol Chem. 1999, 274: 31663-31670. 10.1074/jbc.274.44.31663CrossRefPubMed
27.
Ogunlewe JO, Osegbe DN: Zinc and cadmium concentrations in indigenous blacks with normal, hypertrophic, and malignant prostate. Cancer. 1989, 63: 1388-1392. 10.1002/1097-0142(19890401)63:7<1388::AID-CNCR2820630725>3.0.CO;2-MCrossRefPubMed
28.
Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J: Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med. 1998, 188: 211-216. 10.1084/jem.188.1.211PubMedCentralCrossRefPubMed
29.
Inoue T, Shiraki K, Fuke H, Yamanaka Y, Miyashita K, Yamaguchi Y, Yamamoto N, Ito K, Sugimoto K, Nakano T: Proteasome inhibition sensitizes hepatocellular carcinoma cells to TRAIL by suppressing caspase inhibitors and AKT pathway. Anticancer Drugs. 2006, 17: 261-268. 10.1097/00001813-200603000-00004CrossRefPubMed
30.
Zhao J, Tenev T, Martins LM, Downward J, Lemoine NR: The ubiquitin-proteasome pathway regulates survivin degradation in a cell cycle-dependent manner. J Cell Sci. 2000, 113 (Pt 23): 4363-4371.PubMed
31.
Shumilla JA, Wetterhahn KE, Barchowsky A: Inhibition of NF-kappa B binding to DNA by chromium, cadmium, mercury, zinc, and arsenite in vitro: evidence of a thiol mechanism. Arch Biochem Biophys. 1998, 349: 356-362. 10.1006/abbi.1997.0470CrossRefPubMed
32.
Hyun JS, Satsu H, Shimizu M: Cadmium induces interleukin-8 production via NF-kappaB activation in the human intestinal epithelial cell, Caco-2. Cytokine. 2007, 37: 26-34. 10.1016/j.cyto.2007.02.011CrossRefPubMed
33.
Jeong EM, Moon CH, Kim CS, Lee SH, Baik EJ, Moon CK, Jung YS: Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells. Biochem Biophys Res Commun. 2004, 320: 887-892. 10.1016/j.bbrc.2004.05.218CrossRefPubMed
34.
Giuliano M, Lauricella M, Calvaruso G, Carabillo M, Emanuele S, Vento R, Tesoriere G: The apoptotic effects and synergistic interaction of sodium butyrate and MG132 in human retinoblastoma Y79 cells. Cancer Res. 1999, 59: 5586-5595.PubMed
35.
Golovine K, Makhov P, Uzzo RG, Shaw T, Kunkle D, Kolenko VM: Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo. Clin Cancer Res. 2008, 14: 5376-5384. 10.1158/1078-0432.CCR-08-0455PubMedCentralCrossRefPubMed
36.
Mufti AR, Burstein E, Csomos RA, Graf PC, Wilkinson JC, Dick RD, Challa M, Son JK, Bratton SB, Su GL: XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disorders. Mol Cell. 2006, 21: 775-785. 10.1016/j.molcel.2006.01.033CrossRefPubMed
37.
Freedman LP, Luisi BF, Korszun ZR, Basavappa R, Sigler PB, Yamamoto KR: The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature. 1988, 334: 543-546. 10.1038/334543a0CrossRefPubMed
38.
Altieri DC: Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003, 3: 46-54. 10.1038/nrc968CrossRefPubMed
39.
40.
Makhov P, Golovine K, Uzzo RG, Rothman J, Crispen PL, Shaw T, Scoll BJ, Kolenko VM: Zinc chelation induces rapid depletion of the X-linked inhibitor of apoptosis and sensitizes prostate cancer cells to TRAIL-mediated apoptosis. Cell Death Differ. 2008, 15: 1745-1751. 10.1038/cdd.2008.106PubMedCentralCrossRefPubMed
41.
Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC: Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J. 1999, 18: 5242-5251. 10.1093/emboj/18.19.5242PubMedCentralCrossRefPubMed
42.
Waisberg M, Joseph P, Hale B, Beyersmann D: Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology. 2003, 192: 95-117. 10.1016/S0300-483X(03)00305-6CrossRefPubMed
43.
Joseph P: Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol. 2009, 238: 272-279. 10.1016/j.taap.2009.01.011CrossRefPubMed
44.
Waalkes MP, Diwan BA: Cadmium-induced inhibition of the growth and metastasis of human lung carcinoma xenografts: role of apoptosis. Carcinogenesis. 1999, 20: 65-70. 10.1093/carcin/20.1.65CrossRefPubMed
45.
Waalkes MP, Diwan BA, Weghorst CM, Bare RM, Ward JM, Rice JM: Anticarcinogenic effects of cadmium in B6C3F1 mouse liver and lung. Toxicol Appl Pharmacol. 1991, 110: 327-335. 10.1016/S0041-008X(05)80015-8CrossRefPubMed
46.
Schimmer AD, Welsh K, Pinilla C, Wang Z, Krajewska M, Bonneau MJ, Pedersen IM, Kitada S, Scott FL, Bailly-Maitre B: Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell. 2004, 5: 25-35. 10.1016/S1535-6108(03)00332-5CrossRefPubMed
47.
Belyaeva EA, Dymkowska D, Wieckowski MR, Wojtczak L: Mitochondria as an important target in heavy metal toxicity in rat hepatoma AS-30D cells. Toxicol Appl Pharmacol. 2008, 231: 34-42. 10.1016/j.taap.2008.03.017CrossRefPubMed
48.
Saelens X, Festjens N, Walle LV, van Gurp M, van Loo G, Vandenabeele P: Toxic proteins released from mitochondria in cell death. Oncogene. 2004, 23: 2861-2874. 10.1038/sj.onc.1207523CrossRefPubMed
49.
Althaus J, Siegelin MD, Dehghani F, Cilenti L, Zervos AS, Rami A: The serine protease Omi/HtrA2 is involved in XIAP cleavage and in neuronal cell death following focal cerebral ischemia/reperfusion. Neurochem Int. 2007, 50: 172-180. 10.1016/j.neuint.2006.07.018CrossRefPubMed
50.
Yang QH, Church-Hajduk R, Ren J, Newton ML, Du C: Omi/HtrA2 catalytic cleavage of inhibitor of apoptosis (IAP) irreversibly inactivates IAPs and facilitates caspase activity in apoptosis. Genes Dev. 2003, 17: 1487-1496. 10.1101/gad.1097903PubMedCentralCrossRefPubMed
51.
Yang QH, Du C: Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of XIAP and livin in HeLa cells. J Biol Chem. 2004, 279: 16963-16970. 10.1074/jbc.M401253200CrossRefPubMed
52.
Shi YH, Ding WX, Zhou J, He JY, Xu Y, Gambotto AA, Rabinowich H, Fan J, Yin XM: Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence. Hepatology. 2008, 48: 497-507. 10.1002/hep.22393PubMedCentralCrossRefPubMed
53.
Hwang C, Oetjen KA, Kosoff D, Wojno KJ, Albertelli MA, Dunn RL, Robins DM, Cooney KA, Duckett CS: X-linked inhibitor of apoptosis deficiency in the TRAMP mouse prostate cancer model. Cell Death Differ. 2008, 15: 831-840. 10.1038/cdd.2008.15PubMedCentralCrossRefPubMed
54.
Seligson DB, Hongo F, Huerta-Yepez S, Mizutani Y, Miki T, Yu H, Horvath S, Chia D, Goodglick L, Bonavida B: Expression of X-linked inhibitor of apoptosis protein is a strong predictor of human prostate cancer recurrence. Clin Cancer Res. 2007, 13: 6056-6063. 10.1158/1078-0432.CCR-07-0960CrossRefPubMed
55.
Seeger JM, Brinkmann K, Yazdanpanah B, Haubert D, Pongratz C, Coutelle O, Kronke M, Kashkar H: Elevated XIAP expression alone does not confer chemoresistance. Br J Cancer. 102: 1717-1723.
56.
Albrecht AL, Singh RK, Somji S, Sens MA, Sens DA, Garrett SH: Basal and metal-induced expression of metallothionein isoform 1 and 2 genes in the RWPE-1 human prostate epithelial cell line. J Appl Toxicol. 2008, 28: 283-293. 10.1002/jat.1277CrossRefPubMed
57.
Kolenko VM, Uzzo RG, Dulin N, Hauzman E, Bukowski R, Finke JH: Mechanism of apoptosis induced by zinc deficiency in peripheral blood T lymphocytes. Apoptosis. 2001, 6: 419-429. 10.1023/A:1012497926537CrossRefPubMed
58.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262CrossRefPubMed
59.
Webster LC, Zhang K, Chance B, Ayene I, Culp JS, Huang WJ, Wu FY, Ricciardi RP: Conversion of the E1A Cys4 zinc finger to a nonfunctional His2, Cys2 zinc finger by a single point mutation. Proc Natl Acad Sci USA. 1991, 88: 9989-9993. 10.1073/pnas.88.22.9989PubMedCentralCrossRefPubMed
Metadata
Title
Cadmium down-regulates expression of XIAP at the post-transcriptional level in prostate cancer cells through an NF-κB-independent, proteasome-mediated mechanism
Authors
Konstantin Golovine
Peter Makhov
Robert G Uzzo
Alexander Kutikov
David J Kaplan
Eric Fox
Vladimir M Kolenko
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-183

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