SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity

Lee,Soonduck; Kim,Jinsun; Jung,Samil; Li,Chengping; Yang,Young; Kim,Keun Il; Lim,Jong-Seok; Kim,Yonghwan; Cheon,Choong-Il; Lee,Myeong-Sok

doi:10.3892/ijo.2015.2840

SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity

Authors:
- Soonduck Lee
- Jinsun Kim
- Samil Jung
- Chengping Li
- Young Yang
- Keun Il Kim
- Jong-Seok Lim
- Yonghwan Kim
- Choong-Il Cheon
- Myeong-Sok Lee
View Affiliations

Affiliations: Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea
Published online on: January 13, 2015 https://doi.org/10.3892/ijo.2015.2840
Pages: 1377-1384

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

Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner.

View Figures

View References

1	Du J, Cullen JJ and Buettner GR: Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 1826:443–457. 2012.PubMed/NCBI
2	Head KA: Ascorbic acid in the prevention and treatment of cancer. Altern Med Rev. 3:174–186. 1998.PubMed/NCBI
3	Cameron E and Pauling L: Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 73:3685–3689. 1976. View Article : Google Scholar : PubMed/NCBI
4	Chen Q, Espey MG, Sun AY, et al: Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 105:11105–11109. 2008. View Article : Google Scholar : PubMed/NCBI
5	De Laurenzi V, Melino G, Savini I, Annicchiarico-Petruzzelli M, Finazzi-Agro A and Avigliano L: Cell death by oxidative stress and ascorbic acid regeneration in human neuroectodermal cell lines. Eur J Cancer. 31A:463–466. 1995. View Article : Google Scholar : PubMed/NCBI
6	Verrax J and Calderon PB: Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic Biol Med. 47:32–40. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chen Q, Espey MG, Krishna MC, et al: Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 102:13604–13609. 2005. View Article : Google Scholar : PubMed/NCBI
8	Hoffer LJ, Levine M, Assouline S, et al: Phase I clinical trial of i.v ascorbic acid in advanced malignancy. Ann Oncol. 19:1969–1974. 2008. View Article : Google Scholar : PubMed/NCBI
9	Park S, Ahn ES, Lee S, et al: Proteomic analysis reveals upregulation of RKIP in S-180 implanted BALB/C mouse after treatment with ascorbic acid. J Cell Biochem. 106:1136–1145. 2009. View Article : Google Scholar
10	Belin S, Kaya F, Duisit G, Giacometti S, Ciccolini J and Fontes M: Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression. PLoS One. 4:e44092009. View Article : Google Scholar : PubMed/NCBI
11	Chen Q, Espey MG, Sun AY, et al: Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA. 104:8749–8754. 2007. View Article : Google Scholar : PubMed/NCBI
12	Hong SW, Jin DH, Hahm ES, et al: Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells. Oncol Rep. 18:811–815. 2007.PubMed/NCBI
13	Kim J, Lee SD, Chang B, et al: Enhanced antitumor activity of vitamin C via p53 in cancer cells. Free Radic Biol Med. 53:1607–1615. 2012. View Article : Google Scholar : PubMed/NCBI
14	Hsu SI, Yang CM, Sim KG, Hentschel DM, O’Leary E and Bonventre JV: TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1. EMBO J. 20:2273–2285. 2001. View Article : Google Scholar : PubMed/NCBI
15	Li J, Muscarella P, Joo SH, et al: Dissection of CDK4-binding and transactivation activities of p34(SEI-1) and comparison between functions of p34(SEI-1) and p16(INK4A). Biochemistry. 44:13246–13256. 2005. View Article : Google Scholar : PubMed/NCBI
16	Ried T, Petersen I, Holtgreve-Grez H, et al: Mapping of multiple DNA gains and losses in primary small cell lung carcinomas by comparative genomic hybridization. Cancer Res. 54:1801–1806. 1994.PubMed/NCBI
17	Tang TC, Sham JS, Xie D, et al: Identification of a candidate oncogene SEI-1 within a minimal amplified region at 19q13.1 in ovarian cancer cell lines. Cancer Res. 62:7157–7161. 2002.PubMed/NCBI
18	Hong SW, Shin JS, Lee YM, et al: p34 (SEI-1) inhibits ROS-induced cell death through suppression of ASK1. Cancer Biol Ther. 12:421–426. 2011. View Article : Google Scholar : PubMed/NCBI
19	Hong SW, Kim CJ, Park WS, et al: p34^SEI-1 inhibits apoptosis through the stabilization of the X-linked inhibitor of apoptosis protein: p34^SEI-1 as a novel target for anti-breast cancer strategies. Cancer Res. 69:741–746. 2009. View Article : Google Scholar : PubMed/NCBI
20	Roos-Mattjus P and Sistonen L: The ubiquitin-proteasome pathway. Ann Med. 36:285–295. 2004. View Article : Google Scholar : PubMed/NCBI
21	Ciechanover A and Schwartz AL: The ubiquitin system: pathogenesis of human diseases and drug targeting. Biochim Biophys Acta. 1695:3–17. 2004. View Article : Google Scholar : PubMed/NCBI
22	Komander D and Rape M: The ubiquitin code. Annu Rev Biochem. 81:203–229. 2012. View Article : Google Scholar : PubMed/NCBI
23	Berkers CR and Ovaa H: Drug discovery and assay development in the ubiquitin-proteasome system. Biochem Soc Trans. 38:14–20. 2010. View Article : Google Scholar : PubMed/NCBI
24	Matsuzawa S, Takayama S, Froesch BA, Zapata JM and Reed JC: p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. EMBO J. 17:2736–2747. 1998. View Article : Google Scholar : PubMed/NCBI
25	Roperch JP, Lethrone F, Prieur S, et al: SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: identification of common effectors with p53 and p21(Waf1). Proc Natl Acad Sci USA. 96:8070–8073. 1999. View Article : Google Scholar : PubMed/NCBI
26	Qi J, Kim H, Scortegagna M and Ronai ZA: Regulators and effectors of Siah ubiquitin ligases. Cell Biochem Biophys. 67:15–24. 2013. View Article : Google Scholar : PubMed/NCBI
27	Nemani M, Linares-Cruz G, Bruzzoni-Giovanelli H, et al: Activation of the human homologue of the Drosophila sina gene in apoptosis and tumor suppression. Proc Natl Acad Sci USA. 93:9039–9042. 1996. View Article : Google Scholar : PubMed/NCBI
28	Telerman A and Amson R: The molecular programme of tumour reversion: the steps beyond malignant transformation. Nat Rev Cancer. 9:206–216. 2009. View Article : Google Scholar : PubMed/NCBI
29	Wu H, Lin Y, Shi Y, et al: SIAH-1 interacts with mammalian polyhomeotic homologues HPH2 and affects its stability via the ubiquitin-proteasome pathway. Biochem Biophys Res Commun. 397:391–396. 2010. View Article : Google Scholar : PubMed/NCBI
30	Yoshibayashi H, Okabe H, Satoh S, et al: SIAH1 causes growth arrest and apoptosis in hepatoma cells through beta-catenin degradation-dependent and -independent mechanisms. Oncol Rep. 17:549–556. 2007.PubMed/NCBI
31	Kim SY, Choi DW, Kim EA and Choi CY: Stabilization of HIPK2 by escape from proteasomal degradation mediated by the E3 ubiquitin ligase Siah1. Cancer Lett. 279:177–184. 2009. View Article : Google Scholar : PubMed/NCBI
32	Matsuzawa SI and Reed JC: Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses. Mol Cell. 7:915–926. 2001. View Article : Google Scholar : PubMed/NCBI
33	Matsuo K, Satoh S, Okabe H, et al: SIAH1 inactivation correlates with tumor progression in hepatocellular carcinomas. Genes Chromosomes Cancer. 36:283–291. 2003. View Article : Google Scholar : PubMed/NCBI
34	Winter M, Sombroek D, Dauth I, et al: Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nat Cell Biol. 10:812–824. 2008. View Article : Google Scholar : PubMed/NCBI
35	Herst PM, Broadley KW, Harper JL and McConnell MJ: Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest. Free Radic Biol Med. 52:1486–1493. 2012. View Article : Google Scholar : PubMed/NCBI
36	Kang JS, Cho D, Kim YI, et al: Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake. J Cell Physiol. 204:192–197. 2005. View Article : Google Scholar : PubMed/NCBI
37	Thomas CG, Vezyraki PE, Kalfakakou VP and Evangelou AM: Vitamin C transiently arrests cancer cell cycle progression in S phase and G2/M boundary by modulating the kinetics of activation and the subcellular localization of Cdc25C phosphatase. J Cell Physiol. 205:310–318. 2005. View Article : Google Scholar : PubMed/NCBI
38	Khanna KK, Keating KE, Kozlov S, et al: ATM associates with and phosphorylates p53: mapping the region of interaction. Nat Genet. 20:398–400. 1998. View Article : Google Scholar : PubMed/NCBI
39	Oda K, Arakawa H, Tanaka T, et al: p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell. 102:849–862. 2000. View Article : Google Scholar : PubMed/NCBI
40	Perfettini JL, Castedo M, Nardacci R, et al: Essential role of p53 phosphorylation by p38 MAPK in apoptosis induction by the HIV-1 envelope. J Exp Med. 201:279–289. 2005. View Article : Google Scholar : PubMed/NCBI
41	Kim JE, Jin DH, Lee SD, et al: Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity. Int J Mol Med. 22:651–655. 2008.PubMed/NCBI
42	Cheung HH, LaCasse EC and Korneluk RG: X-linked inhibitor of apoptosis antagonism: strategies in cancer treatment. Clin Cancer Res. 12:3238–3242. 2006. View Article : Google Scholar : PubMed/NCBI
43	Schimmer AD, Dalili S, Batey RA and Riedl SJ: Targeting XIAP for the treatment of malignancy. Cell Death Differ. 13:179–188. 2006. View Article : Google Scholar
44	Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ and Tsang BK: p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer cells. Cancer Res. 63:7081–7088. 2003.PubMed/NCBI
45	Srinivasula SM, Hegde R, Saleh A, et al: A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 410:112–116. 2001. View Article : Google Scholar : PubMed/NCBI
46	Datta R, Oki E, Endo K, Biedermann V, Ren J and Kufe D: XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage. J Biol Chem. 275:31733–31738. 2000. View Article : Google Scholar : PubMed/NCBI
47	Frew IJ, Dickins RA, Cuddihy AR, et al: Normal p53 function in primary cells deficient for Siah genes. Mol Cell Biol. 22:8155–8164. 2002. View Article : Google Scholar : PubMed/NCBI
48	Cardaci S, Filomeni G, Rotilio G and Ciriolo MR: Reactive oxygen species mediate p53 activation and apoptosis induced by sodium nitroprusside in SH-SY5Y cells. Mol Pharmacol. 74:1234–1245. 2008. View Article : Google Scholar : PubMed/NCBI
49	Guo J, Wu G, Bao J, Hao W, Lu J and Chen X: Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner. PLoS One. 9:e881402014. View Article : Google Scholar : PubMed/NCBI
50	Yang J, Wu LJ, Tashino S, Onodera S and Ikejima T: Protein tyrosine kinase pathway-derived ROS/NO productions contribute to G2/M cell cycle arrest in evodiamine-treated human cervix carcinoma HeLa cells. Free Radic Res. 44:792–802. 2010. View Article : Google Scholar : PubMed/NCBI