Neurotoxicity Research

, Volume 9, Issue 1, pp 29–37 | Cite as

Curcumin induces stress response, neurite outgrowth and prevent nf-κb activation by inhibiting the proteasome function

  • Priyanka Dikshit
  • Anand Goswami
  • Amit Mishra
  • Mou Catterjee
  • Nihar Ranjan Jana
Article

Abstract

Curcumin, a natural polyphenolic compound, has long been known as an anti-tumour and anti-inflammatory compound; although, the common mechanism through which it exhibits such properties are remains unclear. Recently, we reported that the curcumin-induced apoptosis is mediated through the impairment of ubiquitin proteasome system (UPS). Here, we show that curcumin disrupts UPS function by directly inhibiting the enzyme activity of the proteasome’s 20S core catalytic component. Like other proteasome inhibitors, curcumin exposure induces neurite outgrowth and the stress response, as evident from the induction of various cytosolic and endoplasmic reticulum chaperones as well as induction of transcription factor CHOP/GADD153. The direct inhibition of proteasome activity also causes an increase in half-life of IκB-α that ultimately leads to the down-regulation of NF-κB activation. These results suggest that curcumin-induced proteasomal malfunction might be linked with both anti-proliferative and anti-inflammatory activities.

Keywords

Curcumin Proteasome IκB NF-κB Stress 

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References

  1. Aggarwal BB, A Kumar and AC Bharti (2003) Anticancer potential of curcumin: preclinical and clinical studies.Anticancer Res. 23, 363–398.PubMedGoogle Scholar
  2. Ammon HP and MA Wahl(1991) Pharmacology ofCurcuma longa. Planta Med. 57, 1–7.CrossRefGoogle Scholar
  3. Bharti AC, N Donato, S Singh and BB Aggarwal (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and IkappaBalpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis.Blood 101, 1053–1062.PubMedCrossRefGoogle Scholar
  4. Bhaumik S, R Anjum, N Rangaraj, BVV Pardhasarradhi and A Khar (1999) Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Lett. 456, 311–314.PubMedCrossRefGoogle Scholar
  5. Bush KT, AL Goldberg and SK Nigam (1997) Proteasome inhibition leads to a heat-shock response, induction of endoplasmic reticulum chaperones, and thermotolerance.J. Biol. Chem. 272, 9086–9092.PubMedCrossRefGoogle Scholar
  6. Chen YR and TH Tan (1998) Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin.Oncogene 17, 173–178.PubMedCrossRefGoogle Scholar
  7. Chuang SE, ML Kuo, CH Hsu, CR Chen, JK Lin, GM Lai, CY Hsieh and AL Cheng (2000) Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis.Carcinogenesis 21, 331–335.PubMedCrossRefGoogle Scholar
  8. Ding Q and JN Keller (2001) Proteasome inhibition in oxidative stress neurotoxicity: implications for heat shock proteins.J. Neurochem. 77, 1010–1017.PubMedCrossRefGoogle Scholar
  9. Drexler HC (1997) Activation of the cell death program by inhibition of proteasome function.Proc. Natl. Acad. Sci. USA,94, 855–860.PubMedCrossRefGoogle Scholar
  10. Drexler HC, W Risau and MA Konerding (2000) Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells.FASEB J. 14, 65–77.PubMedGoogle Scholar
  11. Garg A. and BB Aggarwal (2002) Nuclear transcription factor-kappaB as a target for cancer drug development.Leukemia 16, 1053–1068.PubMedCrossRefGoogle Scholar
  12. Giasson BI, W Bruening, HD Durham and WE Mushynski (1999) Activation of stress-activated protein kinases correlates with neurite outgrowth induced by protease inhibition in PC12 cells.J. Neurochem. 72, 1081–1087.PubMedCrossRefGoogle Scholar
  13. Glickman MH and A Ciechanover (2002) The ubiquitin-protea- some proteolytic pathway: destruction for the sake of construction.Physiol. Rev. 82, 373–428.PubMedGoogle Scholar
  14. Huang TS, SC Lee and JK Lin (1991) Suppression of c-Jun/AP-1 activation by an inhibitor of tumor promotion in mouse fibroblast cells.Proc. Natl. Acad. Sci. USA 88, 5292–5296.PubMedCrossRefGoogle Scholar
  15. Huang MT, YR Lou, W Ma, HL Newmark, KR Reuhland AH Conney (1994) Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice.Cancer Res. 54, 5841–587.PubMedGoogle Scholar
  16. Jana NR, EA Zemskov, G Wang and N Nukina (2001) Altered proteasomal function due to the expression of polyglutamineexpanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochromec release.Hum. Mol. Genet. 10, 1049–1059.PubMedCrossRefGoogle Scholar
  17. Jana NR, P Dikshit, A Goswami and N Nukina (2004) Inhibition of proteasomal function by curcumin induces apoptosis through mitochondrial pathway.J. Biol. Chem. 279, 11680–11685.PubMedCrossRefGoogle Scholar
  18. Khar A, AM Ali, BVV Pardhasaradhi, Z Begum and R Angum (1999) Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells.FEBS Lett. 445, 165–168.PubMedCrossRefGoogle Scholar
  19. Lopes UG, P Erhardt, R Yao and M Cooper (1997) p53-dependent induction of apoptosis by proteasome inhibitors.J. Biol. Chem. 272, 12893–12896.PubMedCrossRefGoogle Scholar
  20. Mehta K, P Pantazis, T McQueen and BB Aggarwal (1997) Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines.Anticancer Drugs 8, 470–481.PubMedCrossRefGoogle Scholar
  21. Meriin AB, VL Gabai, J Aglom, VI Shifrin and MY Sherman (1998) Proteasome inhibitors activate stress kinases and induce Hsp72. Diverse effects on apoptosis.J. Biol. Chem. 273, 6373–6379.PubMedCrossRefGoogle Scholar
  22. Mitsiades N, CS Mitsiades, V Poulaki, D Chauhan, G Fanourakis, X Gu, C Bailey, M Joseph, TA Libermann, SP Treon, NC Munshi, PG Richardson, T Hideshima and KC Anderson (2002) Molecular sequelae of proteasome inhibition in human multiple myeloma cells.Proc. Natl. Acad. Sci. USA 99, 14374–14379.PubMedCrossRefGoogle Scholar
  23. Mullally JE and FA Fitzpatrick (2002) Pharmacophore model for novel inhibitors of ubiquitin isopeptidases that induce p53-independent cell death.Mol. Pharmacol.62, 351–358.PubMedCrossRefGoogle Scholar
  24. Obin M, E Mesco, X Gong, AL Haas, J Joseph and A Taylor (1999) Neurite outgrowth in PC 12 cells. Distinguishing the roles of ubiquitylation and ubiquitin-dependent proteolysis.J. Biol. Chem. 274, 11789–11795.PubMedCrossRefGoogle Scholar
  25. Okada K, C Wangpoengtrakul, T Osawa, S Toyokuni, S Tanaka and K Uchida (1999) Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules.J. Biol. Chem. 274, 23787–23793.PubMedCrossRefGoogle Scholar
  26. Pal S, T Chaudhury, S Chattopadhyay, A Bhattacharya, G Datta, T Das and G Sa (2001) Mechanisms of curcumin-induced apoptosis of Ehrlich’s ascites carcinoma cells.Biochem. Biophys. Res. Commun. 288, 658–665.PubMedCrossRefGoogle Scholar
  27. Sadoul R, PA Fernandez, AL Quiquerez, I Martinou, M Maki, M Schroter, JD Becherer, M Irmler, J Tschopp and JC Martinou (1996) Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons.EMBO J. 15, 3845–3852.PubMedGoogle Scholar
  28. Singh S and BB Aggarwal (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane).J. Biol. Chem. 270, 24995–25000.PubMedCrossRefGoogle Scholar
  29. Wang XZ, M Kuroda, J Sok, N Batchvarova, R Kimmel, P Chung, H Zinszner and D Ron (1998) Identification of novel stress- induced genes downstream of chop.EMBO J. 17, 3619–3630.PubMedCrossRefGoogle Scholar
  30. Woo JH, YH Kim, YJ Choi, DG Kim, KS Lee, JH Bae, S Mindo, JS Cha, YJ Jeong, YH Jee, JW Park and TK Kwon (2003) Molecular mechanisms of curcumin-induced cytotoxicity: induc- tion of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochromec and inhibition of Akt.Carcinogenesis 24, 1199–1208.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • Priyanka Dikshit
    • 1
  • Anand Goswami
    • 1
  • Amit Mishra
    • 1
  • Mou Catterjee
    • 1
  • Nihar Ranjan Jana
    • 1
  1. 1.Cellular and Molecular Neuroscience LaboratoryNational Brain Research CentreManesar, GurgaonIndia

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