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Article

Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells

  • Authors:
    • Yang Wang
    • Ruo-Feng Yin
    • Jia-Song Teng
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Orthopaedics, Daqing Oilfields general Hospital, Daqing, Heilongjiang 163000, P.R. China
  • Pages: 3403-3408
    |
    Published online on: April 20, 2016
       https://doi.org/10.3892/or.2016.4762
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Abstract

The present study was aimed to investigate the effect of tumstatin on inhibition of proliferation and induction of apoptosis in Saos-2 human osteosarcoma cells and to understand the mechanism involved. Inhibition of cell proliferation was analyzed by MTT assay and induction of apoptosis through nuclear fragmentation assay. Viability of Saos-2 cells was reduced to 19% on treatment with 25 µM concentration of tumstatin after 48 h. Presence of characteristic apoptotic nuclei, rounded cell shape and shrunken size were caused by tumstatin treatment at 25 µM concentration. The level of mRNA corresponding to PTEN, FasR and FasL was increased significantly in tumstatin treated Saos-2 cells compared to untreated control. Investigation of the mechanism revealed NF-κB activation by phosphorylation on serine 536. The activated NF-κB was translocated into the nucleus from the cytoplasm on treatment with tumstatin. Degradation of the IκBα by tumstatin was found to be much slower compared to that induced by treatment with TNF-α. Thus, tumstatin inhibits proliferation and induces apoptosis in Saos-2 cells through activation of NF-κB and its translocation to the nucleus. Therefore, tumstatin can play an important role in the treatment of osteosarcoma.
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1 

Tarkkanen M, Karhu R, Kallioniemi A, Elomaa I, Kivioja AH, Nevalainen J, Böhling T, Karaharju E, Hyytinen E, Knuutila S, et al: Gains and losses of DNA sequences in osteosarcomas by comparative genomic hybridization. Cancer Res. 55:1334–1338. 1995.PubMed/NCBI

2 

Al-Romaih K, Bayani J, Vorobyova J, Karaskova J, Park PC, Zielenska M and Squire JA: Chromosomal instability in osteosarcoma and its association with centrosome abnormalities. Cancer Genet Cytogenet. 144:91–99. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Ragland BD, Bell WC, Lopez RR and Siegal GP: Cytogenetics and molecular biology of osteosarcoma. Lab Invest. 82:365–373. 2002. View Article : Google Scholar : PubMed/NCBI

4 

He JP, Hao Y, Wang XL, Yang XJ, Shao JF, Guo FJ and Feng JX: Review of the molecular pathogenesis of osteosarcoma. Asian Pac J Cancer Prev. 15:5967–5976. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Broadhead ML, Clark JC, Myers DE, Dass CR and Choong PF: The molecular pathogenesis of osteosarcoma: A review. Sarcoma. 2011:9592482011. View Article : Google Scholar : PubMed/NCBI

6 

Kansara M and Thomas DM: Molecular pathogenesis of osteosarcoma. DNA Cell Biol. 26:1–18. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Tabone MD, Kalifa C, Rodary C, Raquin M, Valteau-Couanet D and Lemerle J: Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy. J Clin Oncol. 12:2614–2620. 1994.PubMed/NCBI

8 

Kempf-Bielack B, Bielack SS, Jurgens H, Branscheid D, Berdel WE, Exner GU, Göbel U, Helmke K, Jundt G, Kabisch SF, et al: Osteosarcoma relapse after combined modality therapy: An analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol. 23:559–568. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Davis AM, Bell RS and Goodwin PJ: Prognostic factors in osteosarcoma: A critical review. J Clin Oncol. 12:423–431. 1994.PubMed/NCBI

10 

Arends MJ and Wyllie AH: Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol. 32:223–254. 1991. View Article : Google Scholar : PubMed/NCBI

11 

Jacobson MD, Weil M and Raff MC: Programmed cell death in animal development. Cell. 88:347–354. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Cross TG, Scheel-Toellner D, Henriquez NV, Deacon E, Salmon M and Lord JM: Serine/threonine protein kinases and apoptosis. Exp Cell Res. 256:34–41. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Aggarwal BB and Takada Y: Pro-apoptotic and anti-apoptotic effects of tumor necrosis factor in tumor cells. Role of nuclear transcription factor NF-κB. Cancer Treat Res. 126:103–127. 2005. View Article : Google Scholar

14 

Graham B and Gibson SB: The two faces of NF-κB in cell survival responses. Cell Cycle. 4:1342–1345. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Lamkanfi M, Declercq W, Van den Berghe T and Van den Abeele P: Caspases leave the beaten track: caspase-mediated activation of NF-κB. J Cell Biol. 173:165–171. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Piva R, Belardo G and Santoro MG: NF-κB: a stress-regulated switch for cell survival. Antioxid Redox Signal. 8:478–486. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Radhakrishnan SK and Kamalakaran S: Pro-apoptotic role of NF-κB: implications for cancer therapy. Biochim Biophys Acta. 1766:53–62. 2006.PubMed/NCBI

18 

Maeshima Y, Colorado PC, Torre A, Holthaus KA, Grunkemeyer JA, Ericksen MB, Hopfer H, Xiao Y, Stillman IE and Kalluri R: Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J Biol Chem. 275:21340–21348. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Hamano Y and Kalluri R: Tumstatin, the NC1 domain of α3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth. Biochem Biophys Res Commun. 333:292–298. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Pasco S, Brassart B, Ramont L, Maquart FX and Monboisse JC: Control of melanoma cell invasion by type IV collagen. Cancer Detect Prev. 29:260–266. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Pasco S, Ramont L, Venteo L, Pluot M, Maquart FX and Monboisse JC: In vivo overexpression of tumstatin domains by tumor cells inhibits their invasive properties in a mouse melanoma model. Exp Cell Res. 301:251–265. 2004. View Article : Google Scholar : PubMed/NCBI

22 

Kawaguchi T, Yamashita Y, Kanamori M, Endersby R, Bankiewicz KS, Baker SJ, Bergers G and Pieper RO: The PTEN/Akt pathway dictates the direct alphaVbeta3-dependent growth-inhibitory action of an active fragment of tumstatin in glioma cells in vitro and in vivo. Cancer Res. 66:11331–11340. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Chung IS, Son YI, Ko YJ, Baek CH, Cho JK and Jeong HS: Peritumor injections of purified tumstatin delay tumor growth and lymphatic metastasis in an orthotopic oral squamous cell carcinoma model. Oral Oncol. 44:1118–1126. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Tanaka Y, Singh S and Aggarwal BB: Identification of a p65 peptide that selectively inhibits NF-κB activation induced by various inflammatory stimuli and its role in down-regulation of NF-κB-mediated gene expression and up-regulation of apoptosis. J Biol Chem. 279:15096–15104. 2004. View Article : Google Scholar

25 

Fujita M, Goto K, Yoshida K, Okamura H, Morimoto H, Kito S, Fukuda J and Haneji T: Okadaic acid stimulates expression of Fas receptor and Fas ligand by activation of nuclear factor kappa-B in human oral squamous carcinoma cells. Oral Oncol. 40:199–206. 2004. View Article : Google Scholar

26 

Bertram J, Peacock JW, Tan C, Mui AL, Chung SW, Gleave ME, Dedhar S, Cox ME and Ong CJ: Inhibition of the phosphatidylinositol 3′-kinase pathway promotes autocrine Fas-induced death of phosphatase and tensin homologue-deficient prostate cancer cells. Cancer Res. 66:4781–4788. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Yang F, Tang E, Guan K and Wang CY: IKKβ plays an essential role in the phosphorylation of RelA/p65 on serine 536 induced by lipopolysaccharide. J Immunol. 170:5630–5635. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Doyle SL, Jefferies CA and O'Neill LA: Bruton's tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536 during NFκB activation by lipopolysaccharide. J Biol Chem. 280:23496–23501. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Shiraki K, Yamanaka T, Inoue H, Kawakita T, Enokimura N, Okano H, Sugimoto K, Murata K and Nakano T: Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma. Int J Oncol. 26:1273–1281. 2005.PubMed/NCBI

30 

Sakurai H, Chiba H, Miyoshi H, Sugita T and Toriumi W: IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. J Biol Chem. 274:30353–30356. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Madrid LV, Mayo MW, Reuther JY and Baldwin AS Jr: Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem. 276:18934–18940. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Sasaki CY, Barberi TJ, Ghosh P and Longo DL: Phosphorylation of RelA/p65 on serine 536 defines an IκBα-independent NF-κB pathway. J Biol Chem. 280:34538–34547. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Yin R and Teng J: Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells. Oncol Rep 35: 3403-3408, 2016.
APA
Wang, Y., Yin, R., & Teng, J. (2016). Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells. Oncology Reports, 35, 3403-3408. https://doi.org/10.3892/or.2016.4762
MLA
Wang, Y., Yin, R., Teng, J."Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells". Oncology Reports 35.6 (2016): 3403-3408.
Chicago
Wang, Y., Yin, R., Teng, J."Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells". Oncology Reports 35, no. 6 (2016): 3403-3408. https://doi.org/10.3892/or.2016.4762
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Yin R and Teng J: Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells. Oncol Rep 35: 3403-3408, 2016.
APA
Wang, Y., Yin, R., & Teng, J. (2016). Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells. Oncology Reports, 35, 3403-3408. https://doi.org/10.3892/or.2016.4762
MLA
Wang, Y., Yin, R., Teng, J."Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells". Oncology Reports 35.6 (2016): 3403-3408.
Chicago
Wang, Y., Yin, R., Teng, J."Tumstatin induces apoptosis and stimulates phosphorylation of p65NF-κB in human osteoblastic osteosarcoma Saos-2 cells". Oncology Reports 35, no. 6 (2016): 3403-3408. https://doi.org/10.3892/or.2016.4762
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