Sodium orthovanadate induces the apoptosis of SH-SY5Y cells by inhibiting PIWIL2

Tian,Xiaohong; Fan,Jun; Hou,Weijian; Bai,Shuling; Ao,Qiang; Tong,Hao

doi:10.3892/mmr.2015.4616

Sodium orthovanadate induces the apoptosis of SH-SY5Y cells by inhibiting PIWIL2

Authors:
- Xiaohong Tian
- Jun Fan
- Weijian Hou
- Shuling Bai
- Qiang Ao
- Hao Tong
View Affiliations

Affiliations: Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, Liaoning 110122, P.R. China
Published online on: November 26, 2015 https://doi.org/10.3892/mmr.2015.4616
Pages: 874-880

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

PIWIs have been shown to be abnormally expressed in a variety of cancers and may be important in the maintenance and invasion of cancer cells. The high expression of PIWIL2 contributed to the resistance effect of cisplatin in colon cancer cells, and the knockout of the PIWIL2 gene reduced the aggressive nature and malignant degree of colon cancer cells. Sodium orthovanadate (SOV) is a vanadium compound, and exhibited antineoplastic activity in certain types of human cancer cells, including lung, kidney and prostate cancer cells. However, its effects in human neuroblastoma (NB) cells have not yet been reported. The objective of this study was to investigate the effect of SOV on the apoptosis of NB cells and to explore how PIWIL2 is involved in the mechanism underlying this effect. In the present study, SH‑SY5Y cells were treated with SOV and the optimal concentration was determined for further assays. Cell apoptosis, cell count, viability, the cell cycle, and the expression of PIWIL2 mRNA and protein were then determined. The results showed that SOV could induce cell apoptosis, reduce the percentage of viable cells, induce accumulation of SH‑SY5Y cells at the G2/M and S phase of the cell cycle, and inhibit the expression of PIWIL2 and Bcl‑2 mRNA and protein. The results suggested that the underlying mechanisms may be, at least in part, due to SOV inhibiting the expression of PIWIL2. These findings demonstrated the effect of SOV and supported its further evaluation as a treatment for human NB.

View Figures

View References

1	Maris JM and Matthay KK: Molecular biology of neuroblastoma. J Clin Oncol. 17:2264–2279. 1999.PubMed/NCBI
2	Maris JM, Hogarty MD, Bagatell R and Cohn SL: Neuroblastoma. Lancet. 369:2106–2120. 2007. View Article : Google Scholar : PubMed/NCBI
3	Sharp SE, Gelfand MJ and Shulkin BL: Pediatrics: Diagnosis of neuroblastoma. Semin Nucl Med. 41:345–353. 2011. View Article : Google Scholar : PubMed/NCBI
4	Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, et al: Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cisretinoic acid. Children's Cancer group. N Engl J Med. 341:1165–1173. 1999. View Article : Google Scholar : PubMed/NCBI
5	Pearson AD, Pinkerton CR, Lewis IJ, Imeson J, Ellershaw C and Machin D; European Neuroblastoma Study Group, Children's Cancer and Leukaemia Group (CCLG formerly United Kingdom Children's Cancer Study Group): High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: A randomised trial. Lancet Oncol. 9:247–256. 2008. View Article : Google Scholar : PubMed/NCBI
6	Zage PE, Kletzel M, Murray K, Marcus R, Castleberry R, Zhang Y, London WB and Kretschmar C; Children's Oncology Group: Outcomes of the POG 9340/9341/9342 trials for children with high-risk neuroblastoma: A report from the Children's Oncology Group. Pediatr Blood Cancer. 51:747–753. 2008. View Article : Google Scholar : PubMed/NCBI
7	Lau L, Tai D, Weitzman S, Grant R, Baruchel S and Malkin D: Factors influencing survival in children with recurrent neuroblastoma. J Pediatr Hematol Oncol. 26:227–232. 2004. View Article : Google Scholar : PubMed/NCBI
8	Laverdière C, Cheung NK, Kushner BH, Kramer K, Modak S, LaQuaglia MP, Wolden S, Ness KK, Gurney JG and Sklar CA: Long-term complications in survivors of advanced stage neuroblastoma. Pediatr Blood Cancer. 45:324–332. 2005. View Article : Google Scholar : PubMed/NCBI
9	Chen C, Liu J and Xu G: Overexpression of PIWI proteins in human stage III epithelial ovarian cancer with lymph node metastasis. Cancer Biomark. 13:315–321. 2013.
10	Sharma AK, Nelson MC, Brandt JE, Wessman M, Mahmud N, Weller KP and Hoffman R: Human CD34 (+) stem cells express the hiwi gene, a human homologue of the Drosophila gene piwi. Blood. 97:426–434. 2001. View Article : Google Scholar : PubMed/NCBI
11	Carmell MA, Girard A, van de Kant HJ, Bourc'his D, Bestor TH, de Rooij DG and Hannon GJ: MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell. 12:503–514. 2007. View Article : Google Scholar : PubMed/NCBI
12	Aravin A, Gaidatzis D, Pfeffer S, Lagos-Quintana M, Landgraf P, Iovino N, Morris P, Brownstein MJ, Kuramochi-Miyagawa S, Nakano T, et al: A novel class of small RNAs bind to MILI protein in mouse testes. Nature. 442:203–207. 2006.PubMed/NCBI
13	Qiao D, Zeeman AM, Deng W, Looijenga LH and Lin H: Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene. 21:3988–3999. 2002. View Article : Google Scholar : PubMed/NCBI
14	Su C, Ren ZJ, Wang F, Liu M, Li X and Tang H: PIWIL4 regulates cervical cancer cell line growth and is involved in down-regulating the expression of p14ARF and p53. FEBS Lett. 586:1356–1362. 2012. View Article : Google Scholar : PubMed/NCBI
15	Liu C, Qu L, Dong B, Xing X, Ren T, Zeng Y, Jiang B, Meng L, Wu J and Shou C: Combined phenotype of 4 markers improves prognostic value of patients with colon cancer. Am J Med Sci. 343:295–302. 2012. View Article : Google Scholar : PubMed/NCBI
16	Li D, Sun X, Yan D, Huang J, Luo Q, Tang H and Peng Z: Piwil2 modulates the proliferation and metastasis of colon cancer via regulation of matrix metallopeptidase 9 transcriptional activity. Exp Biol Med (Maywood). 237:1231–1240. 2012. View Article : Google Scholar
17	Korbecki J, Baranowska-Bosiacka I, Gutowska I and Chlubek D: Biochemical and medical importance of vanadium compounds. Acta Biochim Pol. 59:195–200. 2012.PubMed/NCBI
18	Wu Y, Ma Y, Xu Z, Wang D, Zhao B, Pan H, Wang J, Xu D, Zhao X, Pan S, et al: Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo. Cancer Lett. 351:108–116. 2014. View Article : Google Scholar : PubMed/NCBI
19	Ipsaro JJ, Haase AD, Knott SR, Joshua-Tor L and Hannon GJ: The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature. 491:279–283. 2012. View Article : Google Scholar : PubMed/NCBI
20	Klein A, Holko P, Ligeza J and Kordowiak AM: Sodium orthovanadate affects growth of some human epithelial cancer cells (A549, HTB44, DU145). Folia Biol (Krakow). 56:115–121. 2008. View Article : Google Scholar
21	Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI
22	Dryer RL and Lata GF: Experimental biochemistry. New York: Oxford University Press; New York, NY: pp. 346–347. 1989
23	Maris JM: Recent advances in neuroblastoma. N Engl J Med. 362:2202–2211. 2010. View Article : Google Scholar : PubMed/NCBI
24	Lee JH, Schütte D, Wulf G, Füzesi L, Radzun HJ, Schweyer S, Engel W and Nayernia K: Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet. 15:201–211. 2006. View Article : Google Scholar
25	Wang QE, Han C, Milum K and Wani AA: Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment. Mutat Res. 708:59–68. 2011. View Article : Google Scholar : PubMed/NCBI
26	Suwalsky M, Fierro P, Villena F, Aguilar LF, Sotomayor CP, Jemiola-Rzeminska M, Strzalka K, Gul-Hinc S, Ronowska A and Szutowicz A: Human erythrocytes and neuroblastoma cells are in vitro affected by sodium orthovanadate. Biochim Biophys Acta. 1818:2260–2270. 2012. View Article : Google Scholar : PubMed/NCBI
27	Kordowiak AM, Klein A, Goc A and Dabroś W: Comparison of the effect of VOSO4, Na3VO4 and NaVO3 on proliferation, viability and morphology of H35-19 rat hepatoma cell line. Pol J Pathol. 58:51–57. 2007.PubMed/NCBI
28	Delwar ZM, Siden A, Cruz MH and Yakisich JS: Menadione: Sodium orthovanadate combination eliminates and inhibits migration of detached cancer cells. ISRN Pharmacol. 2012:3071022012. View Article : Google Scholar
29	Woo ES, Rice RL and Lazo JS: Cell cycle dependent subcellular distribution of Cdc25B subtypes. Oncogene. 18:2770–2776. 1999. View Article : Google Scholar : PubMed/NCBI