Skip to main content

Advertisement

SpringerLink
Log in

Calyculin A causes sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by ROS-mediated down-regulation of cellular FLICE-inhibiting protein (c-FLIP) and by enhancing death receptor 4 mRNA stabilization

  • Original Paper
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Calyculin A (Cal A) is a serine/threonine phosphatase inhibitor that is capable of inducing apoptosis in cancer cells. In this study, we examined whether Cal A could modulate TRAIL-induced apoptosis in human renal carcinoma-derived Caki cells. Our results show that Cal A is capable of sensitizing Caki cells to TRAIL-induced apoptosis, as well as U2OS human osteosarcoma cells and A549 human lung adenocarcinoma epithelial cells. Cal A increases intracellular ROS production and down-regulates c-FLIP(L) expression. Interestingly, the down-regulation of protein phosphatase 1 (PP1) by PP1 siRNA also reduced c-FLIP(L) expression via reactive oxygen species production. Furthermore, Cal A induced death receptor 4 (DR4) mRNA and protein expression by enhancing DR4 mRNA stability. We also found that PP4 siRNA up-regulated DR4 mRNA and protein expression. Collectively, our results suggest that Cal A could enhance TRAIL-mediated apoptosis via the down-regulation of c-FLIP(L) and the up-regulation of DR4 in human renal cell carcinoma cell line Caki.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3(6):673–682

    Article  PubMed  CAS  Google Scholar 

  2. Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277(5327):815–818

    Article  PubMed  CAS  Google Scholar 

  3. Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997) The receptor for the cytotoxic ligand TRAIL. Science 276(5309):111–113

    Article  PubMed  CAS  Google Scholar 

  4. Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277(5327):818–821

    Article  PubMed  CAS  Google Scholar 

  5. Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16(17):5386–5397. doi:10.1093/emboj/16.17.5386

    Article  PubMed  CAS  Google Scholar 

  6. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104(2):155–162. doi:10.1172/jci6926

    Article  PubMed  CAS  Google Scholar 

  7. Leverkus M, Neumann M, Mengling T, Rauch CT, Brocker EB, Krammer PH, Walczak H (2000) Regulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes. Cancer Res 60(3):553–559

    PubMed  CAS  Google Scholar 

  8. Jin Z, McDonald ER 3rd, Dicker DT, El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279(34):35829–35839. doi:10.1074/jbc.M405538200

    Article  PubMed  CAS  Google Scholar 

  9. Kelly MM, Hoel BD, Voelkel-Johnson C (2002) Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Cancer Biol Ther 1(5):520–527

    Article  PubMed  Google Scholar 

  10. Ng CP, Zisman A, Bonavida B (2002) Synergy is achieved by complementation with Apo2L/TRAIL and actinomycin D in Apo2L/TRAIL-mediated apoptosis of prostate cancer cells: role of XIAP in resistance. Prostate 53(4):286–299. doi:10.1002/pros.10155

    Article  PubMed  CAS  Google Scholar 

  11. Walczak H, Bouchon A, Stahl H, Krammer PH (2000) Tumor necrosis factor-related apoptosis-inducing ligand retains its apoptosis-inducing capacity on Bcl-2- or Bcl-xL-overexpressing chemotherapy-resistant tumor cells. Cancer Res 60(11):3051–3057

    PubMed  CAS  Google Scholar 

  12. Zhang Y, Zhang B (2008) TRAIL resistance of breast cancer cells is associated with constitutive endocytosis of death receptors 4 and 5. Mol Cancer Res 6(12):1861–1871. doi:10.1158/1541-7786.mcr-08-0313

    Article  PubMed  CAS  Google Scholar 

  13. McConnell JL, Wadzinski BE (2009) Targeting protein serine/threonine phosphatases for drug development. Mol Pharmacol 75(6):1249–1261. doi:10.1124/mol.108.053140

    Google Scholar 

  14. Shi Y (2009) Serine/threonine phosphatases: mechanism through structure. Cell 139(3):468–484. doi:10.1016/j.cell.2009.10.006

    Article  PubMed  CAS  Google Scholar 

  15. Prickett TD, Brautigan DL (2006) The alpha4 regulatory subunit exerts opposing allosteric effects on protein phosphatases PP6 and PP2A. J Biol Chem 281(41):30503–30511. doi:10.1074/jbc.M601054200

    Google Scholar 

  16. Swingle M, Ni L, Honkanen RE (2007) Small-molecule inhibitors of ser/thr protein phosphatases: specificity, use and common forms of abuse. Methods Mol Biol 365:23–38. doi:10.1385/1-59745-267-X:23

    PubMed  Google Scholar 

  17. Tanaka H, Yoshida K, Okamura H, Morimoto H, Nagata T, Haneji T (2007) Calyculin A induces apoptosis and stimulates phosphorylation of p65NF-kappaB in human osteoblastic osteosarcoma MG63 cells. Int J Oncol 31(2):389–396

    PubMed  CAS  Google Scholar 

  18. Morimoto Y, Ohba T, Kobayashi S, Haneji T (1997) The protein phosphatase inhibitors okadaic acid and calyculin A induce apoptosis in human osteoblastic cells. Exp Cell Res 230(2):181–186. doi:10.1006/excr.1996.3404

    Article  PubMed  CAS  Google Scholar 

  19. Fujita M, Seta C, Fukuda J, Kobayashi S, Haneji T (1999) Induction of apoptosis in human oral squamous carcinoma cell lines by protein phosphatase inhibitors. Oral Oncol 35(4):401–408

    Article  PubMed  CAS  Google Scholar 

  20. Song Q, Lavin MF (1993) Calyculin A, a potent inhibitor of phosphatases-1 and -2A, prevents apoptosis. Biochem Biophys Res Commun 190(1):47–55

    Article  PubMed  CAS  Google Scholar 

  21. Luo Y, Kessel D (1996) The phosphatase inhibitor calyculin antagonizes the rapid initiation of apoptosis by photodynamic therapy. Biochem Biophys Res Commun 221(1):72–76. doi:10.1006/bbrc.1996.0547

    Article  PubMed  CAS  Google Scholar 

  22. Kiss A, Lontay B, Becsi B, Markasz L, Olah E, Gergely P, Erdodi F (2008) Myosin phosphatase interacts with and dephosphorylates the retinoblastoma protein in THP-1 leukemic cells: its inhibition is involved in the attenuation of daunorubicin-induced cell death by calyculin-A. Cell Signal 20(11):2059–2070. doi:10.1016/j.cellsig.2008.07.018

    Article  PubMed  CAS  Google Scholar 

  23. LeBel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5(2):227–231

    Article  PubMed  CAS  Google Scholar 

  24. Lee TJ, Um HJ, Min do S, Park JW, Choi KS, Kwon TK (2009) Withaferin A sensitizes TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP. Free Radic Biol Med 46(12):1639–1649. doi:10.1016/j.freeradbiomed.2009.03.022

  25. Jang JH, Lee TJ, Yang ES, Min do S, Kim YH, Kim SH, Choi YH, Park JW, Choi KS, Kwon TK (2010) Compound C sensitizes Caki renal cancer cells to TRAIL-induced apoptosis through reactive oxygen species-mediated down-regulation of c-FLIPL and Mcl-1. Exp Cell Res 316(13):2194–2203. doi:10.1016/j.yexcr.2010.04.028

  26. Um HJ, Oh JH, Kim YN, Choi YH, Kim SH, Park JW, Kwon TK (2010) The coffee diterpene kahweol sensitizes TRAIL-induced apoptosis in renal carcinoma Caki cells through down-regulation of Bcl-2 and c-FLIP. Chem Biol Interact 186(1):36–42. doi:10.1016/j.cbi.2010.04.013

    Article  PubMed  CAS  Google Scholar 

  27. Sayers TJ, Brooks AD, Koh CY, Ma W, Seki N, Raziuddin A, Blazar BR, Zhang X, Elliott PJ, Murphy WJ (2003) The proteasome inhibitor PS-341 sensitizes neoplastic cells to TRAIL-mediated apoptosis by reducing levels of c-FLIP. Blood 102(1):303–310. doi:10.1182/blood-2002-09-2975

    Article  PubMed  CAS  Google Scholar 

  28. Zhang S, Shen HM, Ong CN (2005) Down-regulation of c-FLIP contributes to the sensitization effect of 3,3′-diindolylmethane on TRAIL-induced apoptosis in cancer cells. Mol Cancer Ther 4(12):1972–1981. doi:10.1158/1535-7163.mct-05-0249

    Article  PubMed  CAS  Google Scholar 

  29. Kim H, Kim EH, Eom YW, Kim WH, Kwon TK, Lee SJ, Choi KS (2006) Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of DR5. Cancer Res 66(3):1740–1750. doi:10.1158/0008-5472.can-05-1568

    Article  PubMed  CAS  Google Scholar 

  30. Chaudhari AA, Seol JW, Kim SJ, Lee YJ, Kang HS, Kim IS, Kim NS, Park SY (2007) Reactive oxygen species regulate Bax translocation and mitochondrial transmembrane potential, a possible mechanism for enhanced TRAIL-induced apoptosis by CCCP. Oncol Rep 18(1):71–76

    PubMed  CAS  Google Scholar 

  31. Kim YH, Jung EM, Lee TJ, Kim SH, Choi YH, Park JW, Choi KS, Kwon TK (2008) Rosiglitazone promotes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by reactive oxygen species-mediated up-regulation of death receptor 5 and down-regulation of c-FLIP. Free Radic Biol Med 44(6):1055–1068. doi:10.1016/j.freeradbiomed.2007.12.001

    Article  PubMed  CAS  Google Scholar 

  32. Yamaguchi M, Sasaki J, Kuwana M, Sakai M, Okamura N, Ishibashi S (1993) Cytosolic protein phosphatase may turn off activated NADPH oxidase in guinea pig neutrophils. Arch Biochem Biophys 306(1):209–214

    Article  PubMed  CAS  Google Scholar 

  33. Forman HJ, Zhou H, Gozal E, Torres M (1998) Modulation of the alveolar macrophage superoxide production by protein phosphorylation. Environ Health Perspect 106(Suppl 5):1185–1190

    Article  PubMed  CAS  Google Scholar 

  34. Dang PM, Raad H, Derkawi RA, Boussetta T, Paclet MH, Belambri SA, Makni-Maalej K, Kroviarski Y, Morel F, Gougerot-Pocidalo MA, El-Benna J (2011) The NADPH oxidase cytosolic component p67phox is constitutively phosphorylated in human neutrophils: regulation by a protein tyrosine kinase, MEK1/2 and phosphatases 1/2A. Biochem Pharmacol 82(9):1145–1152. doi:10.1016/j.bcp.2011.07.070

    Article  PubMed  CAS  Google Scholar 

  35. Frese S, Frese-Schaper M, Andres AC, Miescher D, Zumkehr B, Schmid RA (2006) Cardiac glycosides initiate Apo2L/TRAIL-induced apoptosis in non-small cell lung cancer cells by up-regulation of death receptors 4 and 5. Cancer Res 66(11):5867–5874. doi:10.1158/0008-5472.can-05-3544

    Article  PubMed  CAS  Google Scholar 

  36. Lee JT, Lee TJ, Kim CH, Kim NS, Kwon TK (2009) Over-expression of Reticulon 3 (RTN3) enhances TRAIL-mediated apoptosis via up-regulation of death receptor 5 (DR5) and down-regulation of c-FLIP. Cancer Lett 279(2):185–192. doi:10.1016/j.canlet.2009.01.035

    Article  PubMed  CAS  Google Scholar 

  37. Sun H, Wang Y (2012) Novel Ser/Thr protein phosphatases in cell death regulation. Physiology (Bethesda) 27(1):43–52. doi:10.1152/physiol.00034.2011

    Article  CAS  Google Scholar 

  38. Janssens V, Rebollo A (2012) The role and therapeutic potential of Ser/Thr phosphatase PP2A in apoptotic signalling networks in human cancer cells. Curr Mol Med 12(3):268–287

    Article  PubMed  CAS  Google Scholar 

  39. Tocharus J, Chongthammakun S, Govitrapong P (2008) Melatonin inhibits amphetamine-induced nitric oxide synthase mRNA overexpression in microglial cell lines. Neurosci Lett 439(2):134–137. doi:10.1016/j.neulet.2008.05.036

    Article  PubMed  CAS  Google Scholar 

  40. Inomata M, Saijo N, Kawashima K, Kaneko A, Fujiwara Y, Kunikane H, Tanaka Y (1995) Induction of apoptosis in cultured retinoblastoma cells by the protein phosphatase inhibitor, okadaic acid. J Cancer Res Clin Oncol 121(12):729–738

    Article  PubMed  CAS  Google Scholar 

  41. Goto K, Fukuda J, Haneji T (2002) Okadaic acid stimulates apoptosis through expression of Fas receptor and Fas ligand in human oral squamous carcinoma cells. Oral Oncol 38(1):16–22

    Article  PubMed  CAS  Google Scholar 

  42. Sheikh MS, Garcia M, Zhan Q, Liu Y, Fornace AJ Jr (1996) Cell cycle-independent regulation of p21Waf1/Cip1 and retinoblastoma protein during okadaic acid-induced apoptosis is coupled with induction of Bax protein in human breast carcinoma cells. Cell Growth Differ 7(12):1599–1607

    PubMed  CAS  Google Scholar 

  43. Rami BG, Chin LS, Lazio BE, Singh SK (2003) Okadaic-acid-induced apoptosis in malignant glioma cells. Neurosurg Focus 14(2):e4

    Article  PubMed  Google Scholar 

  44. Haldar S, Jena N, Croce CM (1995) Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 92(10):4507–4511

    Article  PubMed  CAS  Google Scholar 

  45. Benito A, Lerga A, Silva M, Leon J, Fernandez-Luna JL (1997) Apoptosis of human myeloid leukemia cells induced by an inhibitor of protein phosphatases (okadaic acid) is prevented by Bcl-2 and Bcl-X(L). Leukemia 11(7):940–944

    Article  PubMed  CAS  Google Scholar 

  46. Cabado AG, Leira F, Vieytes MR, Vieites JM, Botana LM (2004) Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells. Arch Toxicol 78(2):74–85. doi:10.1007/s00204-003-0505-4

    Article  PubMed  CAS  Google Scholar 

  47. Ravindran J, Gupta N, Agrawal M, Bala Bhaskar AS, Lakshmana Rao PV (2011) Modulation of ROS/MAPK signaling pathways by okadaic acid leads to cell death via, mitochondrial mediated caspase-dependent mechanism. Apoptosis 16(2):145–161. doi:10.1007/s10495-010-0554-0

    Google Scholar 

  48. Chatfield K, Eastman A (2004) Inhibitors of protein phosphatases 1 and 2A differentially prevent intrinsic and extrinsic apoptosis pathways. Biochem Biophys Res Commun 323(4):1313–1320. doi:10.1016/j.bbrc.2004.09.003

    Article  PubMed  CAS  Google Scholar 

  49. Song Q, Baxter GD, Kovacs EM, Findik D, Lavin MF (1992) Inhibition of apoptosis in human tumour cells by okadaic acid. J Cell Physiol 153(3):550–556. doi:10.1002/jcp.1041530316

    Article  PubMed  CAS  Google Scholar 

  50. Ohoka Y, Nakai Y, Mukai M, Iwata M (1993) Okadaic acid inhibits glucocorticoid-induced apoptosis in T cell hybridomas at its late stage. Biochem Biophys Res Commun 197(2):916–921. doi:10.1006/bbrc.1993.2566

    Article  PubMed  CAS  Google Scholar 

  51. Leira F, Vieites JM, Vieytes MR, Botana LM (2001) Apoptotic events induced by the phosphatase inhibitor okadaic acid in normal human lung fibroblasts. Toxicol In Vitro 15(3):199–208

    Article  PubMed  CAS  Google Scholar 

  52. Golstein J, Swillens S, Dumont JE (1995) Comparative cytotoxic effects of two protein phosphatase inhibitors, okadaic acid and calyculin A, on thyroid cells. Cell Death Differ 2(4):321–329

    PubMed  CAS  Google Scholar 

  53. Hong HN, Yoon SY, Suh J, Lee JH, Kim D (2002) Differential activation of caspase-3 at two maturational stages during okadaic acid-induced rat neuronal death. Neurosci Lett 334(1):63–67

    Article  PubMed  CAS  Google Scholar 

  54. Micheau O, Lens S, Gaide O, Alevizopoulos K, Tschopp J (2001) NF-kappaB signals induce the expression of c-FLIP. Mol Cell Biol 21(16):5299–5305. doi:10.1128/mcb.21.16.5299-5305.2001

    Article  PubMed  CAS  Google Scholar 

  55. Panka DJ, Mano T, Suhara T, Walsh K, Mier JW (2001) Phosphatidylinositol 3-kinase/Akt activity regulates c-FLIP expression in tumor cells. J Biol Chem 276(10):6893–6896. doi:10.1074/jbc.C000569200

    Article  PubMed  CAS  Google Scholar 

  56. Fukazawa T, Fujiwara T, Uno F, Teraishi F, Kadowaki Y, Itoshima T, Takata Y, Kagawa S, Roth JA, Tschopp J, Tanaka N (2001) Accelerated degradation of cellular FLIP protein through the ubiquitin-proteasome pathway in p53-mediated apoptosis of human cancer cells. Oncogene 20(37):5225–5231. doi:10.1038/sj.onc.1204673

    Article  PubMed  CAS  Google Scholar 

  57. Zhou XD, Yu JP, Chen HX, Yu HG, Luo HS (2005) Expression of cellular FLICE-inhibitory protein and its association with p53 mutation in colon cancer. World J Gastroenterol 11(16):2482–2485

    PubMed  CAS  Google Scholar 

  58. Ricci MS, Jin Z, Dews M, Yu D, Thomas-Tikhonenko A, Dicker DT, El-Deiry WS (2004) Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity. Mol Cell Biol 24(19):8541–8555. doi:10.1128/mcb.24.19.8541-8555.2004

    Article  PubMed  CAS  Google Scholar 

  59. Lutterbach B, Hann SR (1994) Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. Mol Cell Biol 14(8):5510–5522

    PubMed  CAS  Google Scholar 

  60. Bhatia K, Huppi K, Spangler G, Siwarski D, Iyer R, Magrath I (1993) Point mutations in the c-Myc transactivation domain are common in Burkitt’s lymphoma and mouse plasmacytomas. Nat Genet 5(1):56–61. doi:10.1038/ng0993-56

    Article  PubMed  CAS  Google Scholar 

  61. Henriksson M, Bakardjiev A, Klein G, Luscher B (1993) Phosphorylation sites mapping in the N-terminal domain of c-myc modulate its transforming potential. Oncogene 8(12):3199–3209

    PubMed  CAS  Google Scholar 

  62. Noguchi K, Kitanaka C, Yamana H, Kokubu A, Mochizuki T, Kuchino Y (1999) Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase. J Biol Chem 274(46):32580–32587

    Article  PubMed  CAS  Google Scholar 

  63. Gupta S, Seth A, Davis RJ (1993) Transactivation of gene expression by Myc is inhibited by mutation at the phosphorylation sites Thr-58 and Ser-62. Proc Natl Acad Sci USA 90(8):3216–3220

    Article  PubMed  CAS  Google Scholar 

  64. Li W, Zhang X, Olumi AF (2007) MG-132 sensitizes TRAIL-resistant prostate cancer cells by activating c-Fos/c-Jun heterodimers and repressing c-FLIP(L). Cancer Res 67(5):2247–2255. doi:10.1158/0008-5472.can-06-3793

    Article  PubMed  CAS  Google Scholar 

  65. Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR (1991) Phosphorylation of c-jun mediated by MAP kinases. Nature 353(6345):670–674. doi:10.1038/353670a0

    Article  PubMed  CAS  Google Scholar 

  66. Monje P, Marinissen MJ, Gutkind JS (2003) Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor. Mol Cell Biol 23(19):7030–7043

    Article  PubMed  CAS  Google Scholar 

  67. Park SJ, Sohn HY, Yoon J, Park SI (2009) Down-regulation of FoxO-dependent c-FLIP expression mediates TRAIL-induced apoptosis in activated hepatic stellate cells. Cell Signal 21(10):1495–1503. doi:10.1016/j.cellsig.2009.05.008

    Article  PubMed  CAS  Google Scholar 

  68. Srivastava RK, Unterman TG, Shankar S (2010) FOXO transcription factors and VEGF neutralizing antibody enhance antiangiogenic effects of resveratrol. Mol Cell Biochem 337(1–2):201–212. doi:10.1007/s11010-009-0300-5

    Article  PubMed  CAS  Google Scholar 

  69. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96(6):857–868

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Mid-Career Researcher Program through an NRF grant funded by the MEST (No. 2011-0016239) and Nuclear Research & Development Program of the KOSEF grant funded by MEST (BAERI-M20708630003-07B0863-00310).

Author information

Authors and Affiliations

  1. Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu, 704-701, South Korea

    Seon Min Woo, Kyoung-jin Min & Taeg Kyu Kwon

Authors
  1. Seon Min Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoung-jin Min
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taeg Kyu Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taeg Kyu Kwon.

Additional information

Seon Min Woo and Kyoung-jin Min contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 48 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Woo, S.M., Min, Kj. & Kwon, T.K. Calyculin A causes sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis by ROS-mediated down-regulation of cellular FLICE-inhibiting protein (c-FLIP) and by enhancing death receptor 4 mRNA stabilization. Apoptosis 17, 1223–1234 (2012). https://doi.org/10.1007/s10495-012-0753-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-012-0753-y

Keywords

Search

Navigation