Resveratrol Inhibits Myeloma Cell Growth and Promotes Healthy Bone Marrow

According to recent research from Denmark, Multiple myeloma is characterized by the accumulation of clonal malignant plasma cells in the bone marrow, which stimulates bone destruction by osteoclasts and reduces bone formation by osteoblasts. In turn, the changed bone microenvironment sustains survival of myeloma cells. Therefore, a challenge for treating multiple myeloma is discovering drugs targeting not only myeloma cells but also osteoclasts and osteoblasts.

"Because resveratrol is reported to display antitumor activities on a variety of human cancer cells," wrote P. Boissy and colleagues at South Denmark University Network in Vejle, "we investigated the effects of this natural compound on myeloma and bone cells. We found that resveratrol reduces dose-dependently the growth of myeloma cell lines (RPMI 8226 and OPM-2) by a mechanism involving cell apoptosis."

In cultures of human primary monocytes, resveratrol inhibits dose-dependently receptor activator of nuclear factor-kappa B (NF-kappa B) ligand-induced formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells, TRACP activity in the medium, upregulation of cathepsin K gene expression, and bone resorption, scientists reported.

These inhibitions are associated with a downregulation of RANK expression at both mRNA and cell surface protein levels and a decrease of NFATc1 stimulation and NF-kappa B nuclear translocation, whereas the gene expression of c-fins, CD14, and CD11a is upregulated, the authors said.

Finally, resveratrol promotes dose-dependently the expression of osteoblast markers like osteocalcin and osteopontin in human bone marrow mesenchymal stem cells (hMSC-TERT) and stimulates their response to 1,25(OH)(2) vitamin D-3 [1,25(OH)(2)D-3].

"Moreover," Boissy continued, "resveratrol upregulates dose-dependently the expression of 1,25(OH)(2)D-3 nuclear receptor."

Researchers concluded, Taken together, these results suggest that resveratrol or its derivatives deserve attention as potential drugs for treating multiple myeloma.

Source:

Boissy, et.al. Resveratrol inhibits myeloma cell growth, prevents osteoclast formation, and promotes osteoclast differentiation. Cancer Res, 2005;65(21):9943-9952).

Key concepts: resveratrol, myeloma, chemoprevention