Curcumin, Chemo and Myeloma

Ivana Zavrski, Jan Eucker, Ulrike Heider, Christian Jakob, Claudia Fleissner, Kurt Possinger, Orhan Sezer Hematology and Oncology, Universitaetsklinikum Charite, Berlin, Germany

Curcumin, a polyphenol found in the spice turmeric, is the major yellow pigment used in curries. Curcumin was shown to induce apoptosis in cancer cells and was thought to have a chemopreventive effect. Inactivation of NF-kappaB, inhibition of c-Jun N-terminal kinase, downregulation of cell surface adhesion molecules, cyclin D1, bcl-2 and MMP-9, inhibition of protein kinase C and activation of caspases were the most common effects due to curcumin in tumor cell lines. The aim of this study was to evaluate, whether the addition of curcumin to widely used cytostatic drugs in the treatment of multiple myeloma, e.g. melphalan, doxorubicin and dexamethasone, could enhance or inhibit the induction of apoptosis and could inhibit growth in human multiple myeloma cells. Using the MTT-assay, we found that curcumin inhibits the growth of freshly isolated human bone marrow myeloma cells and myeloma cell lines in a dose dependent manner [10-100 M]. The addition of curcumin to 1M melphalan could slightly increase the apoptosis in all examined cell lines. When curcumin was added to doxorubicin [100, 250 or 1000 nM], we observed a reduced growth inhibition in U266 and LP-1 cells in comparison to doxorubicin alone, and an enhanced growth inhibition in RPMI-S. In all examined cell lines, the addition of 10 M curcumin to 1 or 5 M dexamethasone failed to enhance apoptosis. Interestingly, in freshly isolated myeloma cells from bone marrow aspirates from patients, 100 and 250 nM doxorubicin reduced the pro-apoptotic effect of curcumin. In conclusion, our data show that curcumin inhibits myeloma cell growth and induces apoptosis when applied alone. The addition of curcumin to melphalan increased the pro-apoptotic effect of curcumin, but curcumin antagonized doxorubicin and dexamethasone. The inhibition of doxorubicin-induced apoptosis may be related to the inhibition of reactive oxygen species and c-Jun N-terminal kinase by curcumin. Addition of curcumin to other chemotherapeutic agents should occur with caution.

Abstract #5232 appears in Blood, Volume 102, issue 11, November 16, 2003 Keywords: multiple myeloma|curcumin|apoptosis

For more information concerning curcumin and myeloma, please visit the following patient blog: Margaret's Corner.