TNF-${\alpha}$ Regulates Potassium Cyanate-induced Apoptosis via NF-${\kappa}B$ Activation in HCT 116 Cells

  • Yang, Eun Ju (Department of Clinical Laboratory Science, Daegu Haany University) ;
  • Chang, Jeong Hyun (Department of Clinical Laboratory Science, Daegu Haany University)
  • Received : 2014.03.29
  • Accepted : 2014.03.30
  • Published : 2014.03.31

Abstract

Potassium cyanate (KOCN) that is known as an inducer of the protein carbamylation is an inorganic compound and is the conjugate based of cyanic acid (HOCN). Based on these studies, we confirmed that KOCN induces the apoptosis of the human colorectal cancer cell line, HCT 116 cells, by various mitochondrial pathways. To investigate other mechanisms of KOCN-mediated apoptosis, in the present study, we examined KOCN-induced cytokines production in HCT 116 cells and identified the intracellular signaling pathway in these processes. We first demonstrated that KOCN considerably increased the cell apoptosis via intracellular $Ca^{2+}$ signaling, mitochondrial dysfunction and ROS production. And then we examined TNF-${\alpha}$ and IL-$1{\beta}$ levels mediated by KOCN in HCT 116 cells. Although IL-$1{\beta}$ was not involved in KOCN-mediated HCT 116 cell apoptosis, the release of TNF-${\alpha}$ was mediated by KOCN in HCT 116 cells via NF-${\kappa}B$ activation. Apoptosis was also enhanced by incubation with supernatants from HCT 116 cells after KOCN treatment and this effect was partially reduced by BAY 11-7085 pre-treated supernatant. Taken together, our results indicate that KOCN-induced apoptosis in HCT 116 cells is dependent on the releases of TNF-${\alpha}$ and the increased factors and that the mechanism involves the activation of NF-${\kappa}B$.

Keywords

References

  1. Apostolov EO, Ray Debarti, Alovuia WM, Mikhailova MV, Wang X, Basnakian AG, Shah SV. Endonuclease G mediates endothelial cell death induced by carbamylated LDL. Am J Physiol Heart Circ Physiol. 2011. 300: H1997-H2004. https://doi.org/10.1152/ajpheart.01311.2010
  2. Busquets S, Aranda X, Ribas-Carbo M, Azcon-Bieto J, Lopez- Soriano FJ, Argiles JM. Tumor necrosis factor-alpha uncouples respiration in isolated rat mitochondria. Cytokine. 2003. 22: 1-4. https://doi.org/10.1016/S1043-4666(03)00098-X
  3. Clapham DE. Calcium signaling. Cell. 2007. 131: 1047-1058. https://doi.org/10.1016/j.cell.2007.11.028
  4. Corbett JA, McDaniel ML. Reversibility of interleukin-1 betainduced islet destruction and dysfunction by the inhibition of nitric oxide synthase. Biochem J. 1994. 299: 719-724. https://doi.org/10.1042/bj2990719
  5. Desagher S, Martinou SC. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 2000. 10: 369-377. https://doi.org/10.1016/S0962-8924(00)01803-1
  6. Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002. 82: 47-95.
  7. Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 1999. 13: 1899-1911. https://doi.org/10.1101/gad.13.15.1899
  8. Henriette TL, Guchelaar HJ, Gelderblom H. Pharmacogenetics in chemotherapy of colorectal cancer. Best Pract Res Clin Gastroenterol. 2009. 23: 257-273.
  9. Inoue EN, Nagano I, Ichinohasama R, Asato N, Kondo Y, Iinuma K. Bimodal effects of platelet-derived growth factor on rat mesangial cell proliferation and death, and the role of lysophosphatidic acid in cell survival. Clin Sci (Lond). 2001. 101: 11-19. https://doi.org/10.1042/CS20000293
  10. Ishihama M, Toyooka T, Ibuki Y. Generation of phosphorylated histone H2AX by benzene metabolites. Toxicol in Vitro. 2008. 22: 1861-1868. https://doi.org/10.1016/j.tiv.2008.09.005
  11. Krajewski S, krajewski M, Shabaik A, miyashita T, Wang HE, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. 1994. American J Pathol. 145: 1326-1336.
  12. Kraus LM, Kraus AP. Carbamylation of amino acids and proteins in uremia. Kidney Int. 2001.78: S102-S107.
  13. Kuckel CL, Lubit BW, Lambooy PK, Farnsworth PN. Methylisocyanate and actin polymerization: The in vitro effects of carbamylation. Biochim Biophys Acta. 1993. 1162: 143-148. https://doi.org/10.1016/0167-4838(93)90140-M
  14. Lao Y, Chang DC. Mobilization of $Ca^{2+}$ from endoplasmic reticulum to mitochondria plays a positive role in the early stage of UV- or TNF alpha0induced apoptosis. Biochem Biophys Res Commun. 2008. 373: 42-47. https://doi.org/10.1016/j.bbrc.2008.05.172
  15. OK E, Basnakian AG, Apostolov EO, Barri YM, Shah SV. Carbamylated low-density lipoprotein induces death of endothelial cells: A link to atherosclerosis in patients with kidney disease. Kidney Int. 2005. 68: 173-178. https://doi.org/10.1111/j.1523-1755.2005.00391.x
  16. Rottenberg H, Wu S. Quantitative assay by flow cytometry of the mitochondrial membrane potential in intact cells. Biochim Biophys Acta. 1998. 1404: 393-404. https://doi.org/10.1016/S0167-4889(98)00088-3
  17. Rychahou PG, Kang J, Gulhati P, Doan HQ, Chen LA, Xiao SY, Chung DH, Evers BM. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Nat Acad Sci U S A. 2008. 105: 20315-20320. https://doi.org/10.1073/pnas.0810715105
  18. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem. 2005. 267: 5317-5323.
  19. Terasaka H, Kadoma Y, Sakagami H, Fujisawa S. Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells. Anticancer Res. 2005. 3B: 2241-2247.
  20. Yang EJ, Chang JH. Potassium cyanate induces apoptosis of human colorectal cancer cell via mitochondrial pathway. J Exp Biomed Sci. 2011. 17: 177-184.
  21. Zhu L, Ling S, Yu XD, Venkatesh LK, Subramanian T, Chinnadurai G, Kuo TH. Modulation of mitochondrial $Ca^{2+}$ homeostasis by Bcl-2. J Biol Chem. 1999. 274: 33267-33273. https://doi.org/10.1074/jbc.274.47.33267