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Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism
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 Title & Authors
Arsenic Trioxide Induces Apoptosis and Incapacitates Proliferation and Invasive Properties of U87MG Glioblastoma Cells through a Possible NF-κB-Mediated Mechanism
Ghaffari, Seyed H.; Yousefi, Meysam; Dizaji, Majid Zaki; Momeny, Majid; Bashash, Davood; Zekri, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir;
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 Abstract
Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF- signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF- and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF- down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF--mediated inhibition of survivin and telomerase activity and NF--dependent suppression of cathepsin B, MMP-2 and MMP-9.
 Keywords
Glioblastoma;U87MG;arsenic trioxide;NF-;
 Language
English
 Cited by
 References
1.
Abbas T, Dutta A (2009). p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer, 9, 400-14. crossref(new window)

2.
Baud V, Karin M (2009). Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov, 8, 33-40. crossref(new window)

3.
Bharti AC, Donato N, Singh S, et al (2003). Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-${\kappa}B$ and $I{\kappa}B{\alpha}$ kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood, 101, 1053-62. crossref(new window)

4.
Blazquez C, Salazar M, Carracedo A, et al (2008). Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression. Cancer Res, 68, 1945-52. crossref(new window)

5.
Cao JP, Niu HY, Wang HJ, et al (2013). NF-${\kappa}B$ p65/p52 plays a role in GDNF up-regulating Bcl-2 and Bcl-w expression in 6-OHDA-induced apoptosis of MN9D cell. Int J Neuroscience, 123, 705-10. crossref(new window)

6.
Cerni C (2000). Telomeres, telomerase, and myc. An update. Mutat Res, 462, 31-47. crossref(new window)

7.
Chintala SK, Sawaya R, Aggarwal BB, et al (1998). Induction of matrix metalloproteinase-9 requires a polymerized actin cytoskeleton in human malignant glioma cells. J Biol Chem, 273, 13545-51. crossref(new window)

8.
Cohen KJ, Gibbs IC, Fisher PG, et al (2013). A phase I trial of arsenic trioxide chemoradiotherapy for infiltrating astrocytomas of childhood. Neuro Oncol, 15, 783-7. crossref(new window)

9.
Conway EM, Zwerts F, Van Eygen V, et al (2003). Survivin-dependent angiogenesis in ischemic brain: molecular mechanisms of hypoxia-induced up-regulation. Am J Pathol, 163, 935-46. crossref(new window)

10.
Derudder E, Dejardin E, Pritchard LL, et al (2003). RelB/p50 dimers are differentially regulated by tumor necrosis factor-alpha and lymphotoxin-beta receptor activation: critical roles for p100. J Biol Chem, 278, 23278-84. crossref(new window)

11.
Dizaji MZ, Malehmir M, Ghavamzadeh A, et al (2012). Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line. Neurochem Res, 37, 370-80. crossref(new window)

12.
Endoh T, Tsuji N, Asanuma K, et al (2005a). Survivin enhances telomerase activity via up-regulation of specificity protein 1- and c-Myc-mediated human telomerase reverse transcriptase gene transcription. Experimental Cell Res, 305, 300-11. crossref(new window)

13.
Endoh T, Tsuji N, Asanuma K, et al (2005b). Survivin enhances telomerase activity via up-regulation of specificity protein 1- and c-Myc-mediated human telomerase reverse transcriptase gene transcription. Exp Cell Res, 305, 300-11. crossref(new window)

14.
Gartel AL (2005). The conflicting roles of the cdk inhibitor p21(CIP1/WAF1) in apoptosis. Leuk Res, 29, 1237-8. crossref(new window)

15.
Gritsko T, Williams A, Turkson J, et al (2006). Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res, 12, 11-9. crossref(new window)

16.
Guo M, Mathieu PA, Linebaugh B, et al (2002). Phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor-betaL a process initiated by the exocytosis of cathepsin B. J Biol Chem, 277, 14829-37. crossref(new window)

17.
Harrington HA, Ho KL, Ghosh S, et al (2008). Construction and analysis of a modular model of caspase activation in apoptosis. Theor Biol Med Model, 5, 26. crossref(new window)

18.
Hawkes S, Li H, Taniguchi G (2010). Zymography and Reverse Zymography for Detecting MMPs and TIMPs. Methods Mol Biol, 257-69.

19.
Jing Y, Dai J, Chalmers-Redman RM, et al (1999). Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood, 94, 2102-11.

20.
Kaneuchi M, Yamashita T, Shindoh M, et al (1999). Induction of apoptosis by the p53-273L (Arg --> Leu) mutant in HSC3 cells without transactivation of p21Waf1/Cip1/Sdi1 and bax. Mol Carcinog, 26, 44-52. crossref(new window)

21.
Kang KH, Lee KH, Kim MY, et al (2001). Caspase-3-mediated cleavage of the NF-kappa B subunit p65 at the NH2 terminus potentiates naphthoquinone analog-induced apoptosis. J Biol Chem, 276, 24638-44. crossref(new window)

22.
Li F (2005). Role of survivin and its splice variants in tumorigenesis. Br J Cancer, 92, 212-6. crossref(new window)

23.
Liu W, Gong Y, Li H, et al (2012). Arsenic Trioxide-Induced Growth Arrest of Breast Cancer MCF-7 Cells Involving FOXO3a and IkappaB Kinase beta Expression and Localization. Cancer Biother Radiopharm, 27, 504-12. crossref(new window)

24.
Lo Coco F, Diverio D, Falini B, et al (1999). Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood, 94, 12-22.

25.
Madshus IH (1988). Regulation of intracellular pH in eukaryotic cells. Biochem J, 250, 1-8. crossref(new window)

26.
McLean LA, Roscoe J, Jorgensen NK, et al (2000). Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am J Physiol Cell Physiol, 278, 676-88.

27.
Miller WH Jr., Schipper HM, Lee JS, et al (2002). Mechanisms of action of arsenic trioxide. Cancer Res, 62, 3893-903.

28.
Mitsiades CS, Mitsiades N, Poulaki V, et al (2002). Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications. Oncogene, 21, 5673-83. crossref(new window)

29.
Mohanam S, Jasti SL, Kondraganti SR, et al (2001). Stable transfection of urokinase-type plasminogen activator antisense construct modulates invasion of human glioblastoma cells. Clin Cancer Res, 7, 2519-26.

30.
Mohanam S, Sawaya R, McCutcheon I, et al (1993). Modulation of in vitro invasion of human glioblastoma cells by urokinase-type plasminogen activator receptor antibody. Cancer Res, 53, 4143-7.

31.
Momeny M, Malehmir M, Zakidizaji M, et al (2010a). Silibinin inhibits invasive properties of human glioblastoma U87MG cells through suppression of cathepsin B and nuclear factor kappa B-mediated induction of matrix metalloproteinase 9. Anticancer Drugs, 21, 252-60. crossref(new window)

32.
Momeny M, Zakidizaji M, Ghasemi R, et al (2010b). Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin. Med Oncol, 27, 833-42. crossref(new window)

33.
Morales AA, Gutman D, Lee KP, et al (2008). BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma. Blood, 111, 5152-62. crossref(new window)

34.
Nagai S, Washiyama K, Kurimoto M, et al (2002). Aberrant nuclear factor-kappaB activity and its participation in the growth of human malignant astrocytoma. J Neurosurg, 96, 909-17. crossref(new window)

35.
Nakada M, Nakada S, Demuth T, et al (2007). Molecular targets of glioma invasion. Cell Mol Life Sci, 64, 458-78. crossref(new window)

36.
Nicholson DW, Ali A, Thornberry NA, et al (1995). Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 376, 37-43. crossref(new window)

37.
Pennati M, Folini M, Zaffaroni N (2008). Targeting survivin in cancer therapy. Expert Opinion Therapeutic Targets, 12, 463-76. crossref(new window)

38.
Pettersson HM, Pietras A, Munksgaard Persson M, et al (2009). Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells. Mol Cancer Ther, 8, 160-70. crossref(new window)

39.
Pomerantz JL, Baltimore D (2002). Two pathways to NF-kappaB. Mol Cell, 10, 693-5. crossref(new window)

40.
Porter AG, Janicke RU (1999). Emerging roles of caspase-3 in apoptosis. Cell Death Differ, 6, 99-104. crossref(new window)

41.
Rao JS (2003). Molecular mechanisms of glioma invasiveness: the role of proteases. Nature reviews. Cancer, 3, 489-501.

42.
Ryan BM, O’Donovan N, Duffy MJ (2009). Survivin: A new target for anti-cancer therapy. Cancer Treat Rev, 35, 553-62. crossref(new window)

43.
Samuels-Lev Y, O'Connor DJ, Bergamaschi D, et al (2001). ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell, 8, 781-94. crossref(new window)

44.
Sanz MA, Fenaux P, Lo Coco F (2005). Arsenic trioxide in the treatment of acute promyelocytic leukemia. A review of current evidence. Haematologica, 90, 1231-5.

45.
Shou Y, Li N, Li L, et al (2002). NF-kappaB-mediated up-regulation of Bcl-X(S) and Bax contributes to cytochrome c release in cyanide-induced apoptosis. J Neurochem, 81, 842-52. crossref(new window)

46.
Siu KP, Chan JY, Fung KP (2002). Effect of arsenic trioxide on human hepatocellular carcinoma HepG2 cells: inhibition of proliferation and induction of apoptosis. Life Sci, 71, 275-85. crossref(new window)

47.
Sun C, Wang Q, Zhou H, et al (2013). Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo. Neuroscience Bulletin, 29, 83-93. crossref(new window)

48.
Tallman MS (2001). Arsenic trioxide: its role in acute promyelocytic leukemia and potential in other hematologic malignancies. Blood Rev, 15, 133-42. crossref(new window)

49.
Tirapelli LF, Bolini PH, Tirapelli DP, et al (2010). Caspase-3 and Bcl-2 expression in glioblastoma: an immunohistochemical study. Arq Neuropsiquiatr, 68, 603-7. crossref(new window)

50.
Vuky J, Yu R, Schwartz L, et al (2002). Phase II trial of arsenic trioxide in patients with metastatic renal cell carcinoma. Invest New Drugs, 20, 327-30. crossref(new window)

51.
Wang M, Wang T, Liu S, et al (2003). The expression of matrix metalloproteinase-2 and-9 in human gliomas of different pathological grades. Brain Tumor Pathol, 20, 65-72. crossref(new window)

52.
Ware ML, Berger MS, Binder DK (2003). Molecular biology of glioma tumorigenesis. Histol Histopathol, 18, 207-16.

53.
Wei LH, Lai KP, Chen CA, et al (2005). Arsenic trioxide prevents radiation-enhanced tumor invasiveness and inhibits matrix metalloproteinase-9 through downregulation of nuclear factor kappaB. Oncogene, 24, 390-8. crossref(new window)

54.
Westhoff M-A, Zhou S, Nonnenmacher L, et al (2013). Inhibition of NF-${\kappa}B$ Signaling Ablates the Invasive Phenotype of Glioblastoma. Molecular Cancer Res.

55.
Wojtyla A, Gladych M, Rubis B (2011). Human telomerase activity regulation. Mol Biol Rep, 38, 3339-49. crossref(new window)

56.
Yoo H, Sohn S, Nam BH, et al (2010). The expressions of carbonic anhydrase 9 and vascular endothelial growth factor in astrocytic tumors predict a poor prognosis. Int J Mol Med, 26, 3-9.

57.
Yu J, Qian H, Li Y, et al (2007). Arsenic trioxide (As2O3) reduces the invasive and metastatic properties of cervical cancer cells in vitro and in vivo. Gynecol Oncol, 106, 400-6. crossref(new window)

58.
Zanotto-Filho A, Braganhol E, Schroder R, et al (2011). NFkappaB inhibitors induce cell death in glioblastomas. Biochem Pharmacol, 81, 412-24. crossref(new window)

59.
Zarnescu O, Brehar FM, Chivu M, et al (2008). Immunohistochemical localization of caspase-3, caspase-9 and Bax in U87 glioblastoma xenografts. J Mol Histol, 39, 561-9. crossref(new window)

60.
Zhang X, Bu XY, Zhen HN, et al (2000). Expression and localisation of urokinase-type plasminogen activator gene in gliomas. J Clin Neurosci, 7, 116-9. crossref(new window)