Skip to main content
SpringerLink
Log in

Curcumin inhibits ultraviolet light induced human immunodeficiency virus gene expression

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Recently, we reported that the herbal drug St. John's Wort is a potent inhibitor of UV-induced HIV-LTR activation in stably transfected HIVcat/HeLa cells [35]. Our previous studies have demonstrated that the activation of p38 MAP kinase (stress-activated protein kinase-2) and NF-κB are both required for a full UV-induced HIV gene expression response. In this study we have investigated the mechanism by which curcumin inhibits UV-activated HIV-LTR gene expression. We found that treatment of HIVcat/HeLa cells with micromolar concentrations of curcumin completely abolished UV activation of HIV gene expression. Curcumin treatment at similar doses as those used to inhibit HIV gene expression also effectively blocked UV activation of NF-κB, as demonstrated by electrophoretic mobility shift assay. In contrast, curcumin did not inhibit UV-induced phosphorylation of p38 MAP kinase. This observation was also supported by findings that curcumin did not inhibit UV-induced phosphorylation of CREB/ATF-1 and ATF-2. Although curcumin was ineffective in preventing UV-induced p44/42 MAP kinase phosphorylation, the JNK (1 and 2) and AP-1 activation were efficiently blocked by curcumin in HeLa cells. We conclude that the mechanism by which curcumin modulates UV activation of HIV-LTR gene expression mainly involves the inhibition of NF-κB activation.

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

Similar content being viewed by others

References

  1. Araujo CC, Leon LL: Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 96: 723-728, 2001

    Google Scholar 

  2. Lodha R, Bagga A: Traditional Indian system of medicine. Ann Acad Med Singapore 29: 37-41, 2000

    Google Scholar 

  3. De Clercq E: Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med Res Rev 20: 323-349, 2000

    Google Scholar 

  4. Huang MT, Ma W, Yen P, Xie JG, Han J, Frenkel K, Grunberger D, Conney AH: Inhibitory effects of topical application of low doses of curcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and oxidized DNA bases in mouse epidermis. Carcinigenesis 18: 83-88, 1997

    Google Scholar 

  5. Xu YX, Pindolia KR, Janakiraman N, Chapman RA, Gautam SC: Curcumin inhibits IL1 and TNF-alpha induction of AP-1 and NF-κB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 11: 49-62, 1997–1998

    Google Scholar 

  6. Chan MM, Huang HI, Fenton MR, Fong D: In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol 55: 1955-1962, 1998

    Google Scholar 

  7. Zhang F, Altori NK, Mestre JR, Subbaramaiah K, Dannenberg AJ: Curcumin inhibits cyclooxygenase-2 transcription in bile acid-and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis 20: 445-451, 1999

    Google Scholar 

  8. Liu JY, Lin SJ, Lin JK: Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells. Carcinogenesis 14: 857-861, 1993

    Google Scholar 

  9. Hasmeda M, Polya GM: Inhibition of cyclic AMP-dependent protein kinase by curcumin. Phytochemistry 42: 599-605, 1996

    Google Scholar 

  10. Chen YR, Tan TH: Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17: 173-178, 1998

    Google Scholar 

  11. Korutla L, Kumar R: Inhibitory effects of curcumin on epidermal growth factor receptor kinase activity in A431 cells. Biochim Biophys Acta 1224: 597-600, 1994

    Google Scholar 

  12. Seger R, Krebs EG: The MAPK signaling cascade. FASEB J 9: 726-735, 1995

    Google Scholar 

  13. Davis RJ: The mitogen-activated protein kinase signal transduction pathway. J Biol Chem 268: 14553-14556, 1993

    Google Scholar 

  14. Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ: Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270: 7420-7426, 1995

    Google Scholar 

  15. Ip YT, Davis RJ: Signal transduction by the c-jun-N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol 10: 205-219, 1998

    Google Scholar 

  16. Hill CS, Treisman R: Transcriptional regulation by extra cellular signals: Mechanisms and specificity. Cell 80: 199-211, 1995

    Google Scholar 

  17. Kyriakis JM, Avruch J: Protein kinase cascades activated by stress and inflammatory cytokines. Bioassays 18: 567-577, 1996

    Google Scholar 

  18. Baldassare JJ, Bi Y, Bellone CJ: The role of p38MAPK in IL-1β transcription. J Immunol 162: 5367-5373, 1999

    Google Scholar 

  19. Buschmann T, Yin Z, Bhoumik A, Ronai Z: Amino-terminal-derived JNK fragment alters expression and activity of c-jun, ATF2, and p53 and increases H2O2-induced cell death. J Biol Chem 275: 16590-16596, 2000

    Google Scholar 

  20. Chen P, Flory E, Avots A, Jordan BWM, Kirchhoff F, Ludwig S, Rapp UR: Transactivation of naturally occurring HIV-1 long terminal repeats by the JNK signaling pathway: The most frequent naturally occurring length polymorphism sequence introduces a novel binding site for AP-1 factors. J Biol Chem 27: 20382-20390, 2000

    Google Scholar 

  21. Taher MM, Baumgardner T, Dent P, Valerie KC: Genetic evidence that stress-activated p38 MAP kinase is necessary but not sufficient for UV activation of HIV gene expression. Biochemistry 38: 13055-13062, 1999

    Google Scholar 

  22. Taher MM, Oakley JD, Hershey CM, Valerie KC: Activation of NF-κB and p38 MAP kinase is not sufficient for triggering efficient HIV gene expression in response to stress. Biochemistry 39: 1709-1715, 2000

    Google Scholar 

  23. Taher MM, Hershey CM, Oakley JD, Valerie KC: Role of the p38 and MEK-1 and2/p44/42 MAP kinase pathways in the differential activation of human immunodeficiency virus gene expression by ultraviolet and ionizing radiation. Photochem Photobiol 71: 455-459, 2000

    Google Scholar 

  24. Schmidt-Ullrich RK, Dent P, Grant S, Mikkelsen RB, Valerie K: Signal transduction and cellular radiation responses. Radiat Res 153: 245-257, 2000

    Google Scholar 

  25. Huang C, Ma W, Li J, Dong Z: Arsenic induces apoptosis through a c-Jun NH2-terminal kinase dependent, p53 independent pathway. Cancer Res 59: 3053-3058, 1999

    Google Scholar 

  26. van Dam H, Wilhelm D, Herr I, Steffen A, Herrlich P, Angel P: ATF-2 is preferentially activated by stress-activated protein kinases to mediate c-jun induction in response to genotoxic agents. EMBO J 14: 1798-1811, 1995

    Google Scholar 

  27. Dhanwada KR, Dickens M, Neades R, Davis RJ, Pelling JC: Differential effects of UV-B and UV-C components of solar radiation on MAP kinase signal transduction pathways in epidermal keratinocytes. Oncogene 11: 1947-1953, 1995

    Google Scholar 

  28. Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB: Tumor necrosis factor α activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-κB sites in the long terminal repeat. Proc Natl Acad Sci USA 86: 5974-5978, 1989

    Google Scholar 

  29. Nabel G, Baltimore D: An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature (London) 326: 711-713, 1987

    Google Scholar 

  30. Dinter H, Chiu R, Imagawa M, Karin M, Jones KA: In vitro activation of the HIV-1 enhancer in extracts from cells treated with a phorbol ester tumor promoter. EMBO J 6: 4067-4071, 1987

    Google Scholar 

  31. Maio JJ, Brown FL: Regulation of expression driven by human immunodeficiency virus type 1 and human T-cell leukemia virus type I long terminal repeats in pluripotential human embryonic cells. J Virol 62: 1398-1407, 1988

    Google Scholar 

  32. Tong-Starksen SE, Luciw PA, Peterlin BM: Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat. J Immunol 142: 702-707, 1989

    Google Scholar 

  33. Kumar S, Orsini MJ, Lee JC, McDonnell PC, Debouck C, Young PR: The activation of the HIV-1 Long terminal repeat induced by cytokines and environmental stress requires an active p38 MAP kinase. J Biol Chem 271: 30864-30869, 1996

    Google Scholar 

  34. Cohen PS, Schmidtmayerova H, Dennis J, Dubrovsky L, Sherry B, Wang H, Bukrinsky M, Tracey KJ: The critical role of p38 MAP kinase in T cell HIV-1 replication. Mol Med 3: 339-346, 1997

    Google Scholar 

  35. Taher MM, Lammering G, Hershey CM, Valerie KC: Mood enhancing antidepressant St. John's Wort inhibits the activation of human immunodeficiency virus gene expression by ultraviolet light. IUBMB Life 54: 357-364, 2003

    Google Scholar 

  36. Valerie K, Delers A, Bruck C, Thiriart C, Rosenberg H, Debouck C, Rosenberg M: Activation of human immunodeficiency virus type 1 by DNA damage in human cells. Nature (London) 333: 78-81, 1988

    Google Scholar 

  37. Valerie K Laster WS Kirkham JC Kuemmerle NB: Ionizing radiation activates nuclear factor κB but fails to produce an increase in human immunodeficiency virus gene expression in stably transfected human cells. Biochemistry 34: 15768-15776, 1995.

    Google Scholar 

  38. Shapiro L, Heidenreich KA, Meintzer MK, Dinarello CA: Role of p38 mitogen-activated protein kinase in HIV type-1 production in vitro. Proc Natl Acad Sci USA 95: 7422-7426, 1998

    Google Scholar 

  39. Breithaupt TB, Vazquez A, Baez I, Eylar EH: The suppression of T cell function and NF-κB expression by serine protease inhibitors is blocked by N-acetylcysteine. Cell Immunol 173: 124-130, 1996

    Google Scholar 

  40. Butera ST: Therapeutic targeting of human immunodeficiency virus type-1 latency: Current clinical realities and future scientific possibilities. Antiviral Res 48: 143-176, 2000

    Google Scholar 

  41. Gaynor R: Cellular transcription factors involved in the regulation of HIV-1 gene expression. AIDS 6: 347-363, 1992

    Google Scholar 

  42. Dasgupta P, Saikumar P, Reddy CD, Reddy EP: Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription. Proc Natl Acad Sci USA 87: 8090-8094, 1990

    Google Scholar 

  43. Klaver B, Berkhout B: Comparison of 5′ and 3′ long terminal repeat promoter function in human immunodeficiency virus. J Virol 68: 3830-3840, 1994

    Google Scholar 

  44. Perkins ND, Edwards NL, Duckett CS, Agranoff AB, Schmidt RM, Nabel GI: A cooperative interaction between NF-κB and Sp1 is required for HIV-1 enhancer activation. EMBO J 12: 3551-3558, 1994

    Google Scholar 

  45. Griffin GE, Leung D, Folks TM, Kunkel S, Nabel GJ: Activation of HIV gene expression during monocyte differentiation by induction of NF-κB. Nature (London) 339: 70-73, 1989

    Google Scholar 

  46. Barbeau B, Bernier R, Dumais N, Briand G, Olivier M, Faure R, Posner BI, Tremblay M: Activation of HIV-1 long terminal repeat transactivation and virus replication via NF-κB-dependent and-independent pathways by potent phosphotyrosine phosphatase inhibitors, the peroxovanadium compounds. J Biol Chem 272: 12968-12977, 1997

    Google Scholar 

  47. Khar A, Ali AM, Pardhasaradhi BV, Begum Z, Anjum R: Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells. FEBS Lett 445: 165-168: 1999

    Google Scholar 

  48. Woloschak GE, Schreck S, Panozo J, Chang-Liu CM, Libertin CR: HIV expression is induced in dying cells. Biochem Biophys Acta 1351: 105-110, 1997

    Google Scholar 

  49. Oakley JD, Taher MM, Hershey C, Aggarwal PC, Estwani IB, Valerie K: Triggering of apoptosis is not sufficient to increase HIV gene expression: Separation of apoptosis and gene expression in response to UV. IUBMB, 2003 (in press)

  50. Doppler C, Schalasta G, Amtmann E, Sauer G: Binding of NF-κB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity. AIDS Res Hum Retroviruses 8: 245-252, 1992

    Google Scholar 

  51. Yang X, Chen Y, Gabuzda D: ERK MAP kinase links cytokine signals to activation of latent HIV-1 infection by stimulating a cooperative interaction of AP-1 and NF-κB. J Biol Chem 274: 27981-27988, 1999

    Google Scholar 

  52. Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, Pardee AB: Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. Proc Natl Acad Sci USA 90: 1839-1842, 1993

    Google Scholar 

  53. Barthelemy S, Vergnes L, Moynier M, Guyot D, Labidalle S, Bahraoui E: Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat. Res Virol 149: 43-52, 1998

    Google Scholar 

  54. Bremner P Heinrich M: Natural products as targeted modulators of the nuclear factor-kappaB pathway. J Pharm Pharmacol 54: 453-472, 2002

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Neurology and Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, USA

    Mohiuddin M. Taher

  2. Department of Radiation Oncology, Heinrich-Heine University, Duesseldorf, Germany

    Guido Lammering

  3. Radiation Oncology, Virginia Commonwealth University, Richmond, VA, USA

    Chad Hershey & Kristoffer Valerie

Authors
  1. Mohiuddin M. Taher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guido Lammering
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chad Hershey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kristoffer Valerie
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taher, M.M., Lammering, G., Hershey, C. et al. Curcumin inhibits ultraviolet light induced human immunodeficiency virus gene expression. Mol Cell Biochem 254, 289–297 (2003). https://doi.org/10.1023/A:1027393719610

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027393719610

Search

Navigation