Treatment of Human Multiple Myeloma by Curcumin

Abstract

All multiple myeloma cell lines examined showed constitutively active IκB kinase (IKK), IκBα phosphorylation and constitutively active NF-κB. Curcumin, a chemopreventive agent, suppressed constitutive IκBα phosphorylation through inhibition of IKK activity and downregulated NF-κB. Curcumin also downregulated expression of NF-κB-regulated gene products such as IκBα, Bcl-2, Bcl-x L , cyclin D1 and interleukin-6. Consequently, curcumin suppressed multiple myeloma cell proliferation and arrested cells at the G1/S phase of the cell cycle. Curcumin also induced apoptosis and chemosensitivity to vincristine. Overall, results presented herein provide a molecular basis for the treatment of multiple myeloma patients with this pharmacologically safe agent.

1 - 13 . (canceled)  
     
     
         14 . A method of inducing chemosensitivity in chemoresistant multiple myeloma cells in vitro or in vivo, comprising contacting said cells with an amount of a curcuminoid effective to induce chemosensitivity in said cells.  
     
     
         15 . The method of  claim 14 , wherein said cells are in vivo.  
     
     
         16 . The method of  claim 14 , wherein said chemoresistant multiple myeloma cells are chemoresistant to a chemotherapeutic agent selected from the group consisting of vincristine, BCNU, melphalan, cyclophosphamide, Adriamycin, prednisone, velcade, thalidomide, and dexamethasone.  
     
     
         17 . The method of  claim 14 , wherein said multiple myeloma cells are CD138.sup.+plasma cells.  
     
     
         18 . A method of inducing chemosensitivity to one or more chemotherapeutic agents against multiple myeloma cells in a subject, comprising the steps of: 
 a) administering to said subject a curcuminoid, and    b) administering to said subject one or more chemotherapeutic agents,    wherein said curcuminoid induces chemosensitivity to said one or more chemotherapeutic agents against multiple myeloma cells in said individual.    
     
     
         19 . The method of  claim 18 , wherein said subject is a human.  
     
     
         20 . The method of  claim 18 , wherein said one or more chemotherapeutic agents are selected from the group consisting of vincristine, BCNU, melphalan, cyclophosphamide, Adriamycin, prednisone, velcade, thalidomide, and dexamethasone.  
     
     
         21 . The method of  claim 18 , wherein said curcuminoid is administered orally.  
     
     
         22 . The method of  claim 18 , wherein said curcuminoid is administered in a dose of from about 0.01 mg/kg of the subject's body weight to about 500 mg/kg of the subject's body weight.  
     
     
         23 . The method of  claim 18 , wherein said multiple myeloma cells are CD138.sup.+plasma cells.