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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-05-1320. This Article Full Text (PDF) All Versions of this Article: 2002-05-1320v1 101/3/1053    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bharti, A. C Articles by Aggarwal, B. B Search for Related Content PubMed PubMed Citation Articles by Bharti, A. C Articles by Aggarwal, B. B Social Bookmarking                   What's this? Submitted May 6, 2002 Accepted August 26, 2002 Curcumin (Diferuloylmethane) downregulates the constitutive activation of nuclear factor B and IB kinase in human multiple myeloma cells leading to suppression of proliferation and induction of apoptosis Alok C Bharti, Nicholas Donato, Sujay Singh, and Bharat B Aggarwal* Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA Imgenex, San Diego, CA, USA * Corresponding author; email: aggarwal{at}mdanderson.org. Because of the central role of the nuclear transcription factor NF-B in cell survival and proliferation in human multiple myeloma (MM), we explored the possibility of using it as a target for MM treatment by using curcumin (diferuloylmethane) an agent known to have very little or no toxicity in humans. We found that NF-B was constitutively active in all human MM cell lines examined and that curcumin, a chemopreventive agent, downregulated NF-B in all cell lines as indicated by electrophoretic mobility gel shift assay and prevented the nuclear retention of p65 as shown by immunocytochemistry. All MM cell lines showed consitutively active IB kinase (IKK) and IB phosphorylation. Curcumin suppressed the constitutive IkBa phosphorylation through the inhibition of IKK activity. Curcumin also downregulated the expression of NF-B-regulated gene products including IB, Bcl-2, Bcl-xL, cyclin D1 and interleukin-6. This led to the suppression of proliferation and arrest of cells at the G1/S phase of the cell cycle. Suppression of NF-B complex by IKK/NF-B essential modulator-binding domain peptide also suppressed the proliferation of MM cells. Curcumin also activated caspase-7 and caspase-9 and induced PARP cleavage. Curcumin-induced downregulation of NF-B, a factor that has been implicated in chemoresistance, also induced chemosensitivity to vincristine and melphalan. Overall, our results indicate that curcumin downregulates NF-B in human MM cells, leading to the suppression of proliferation and induction of apoptosis; thus providing the molecular basis for the treatment of MM patients with this pharmacologically safe agent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. M. Kamat, S. T. Tharakan, B. Sung, and B. B. Aggarwal Curcumin Potentiates the Antitumor Effects of Bacillus Calmette-Guerin against Bladder Cancer through the Downregulation of NF-{kappa}B and Upregulation of TRAIL Receptors Cancer Res., December 1, 2009; 69(23): 8958 - 8966. [Abstract] [Full Text] [PDF] T. Golombick, T. H. Diamond, V. Badmaev, A. Manoharan, and R. 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