October 14th 2008 post: A couple of blog readers, thanks!, as well as a Google Alert, informed me of a new study on multiple myeloma, bortezomib (=Velcade) and curcumin, which Sherlock (grazie!) found and sent to me.
It was published in Molecular Oncology in September. You can view the abstract here: http://tinyurl.com/3uc8bl Important things: curcumin stopped myeloma cells and bone marrow stromal cells (BMSCs) from producing pro-inflammatory cytokines and VEGF, which are associated with myeloma progression and resistance to chemotherapy. (BMSCs are crucial for myeloma cell growth and survival.) The main message is that curcumin increases the therapeutic efficacy of bortezomib in myeloma. Sounds good.
On to the full study, now: to achieve high response rates in relapsed MM patients, various combinations of bortezomib plus conventional agents […] have been used successfully in clinical trials. Researchers in general, the study tells us, are looking for other substances to test with bortezomib. In this study the most promising substance turned out to be curcumin.
Something I did not know: the effects of curcumin on bone marrow stromal cells (BMSCs) interacting with MM cells in bone marrow microenvironments has not been investigated. So the researchers tested these effects on myeloma cells alone or co-cultured with BMSCs. In the first 24 hours nothing good happened, that is, myeloma cell proliferation continued. In fact, in the presence of BMSCs, the proliferation accelerated. But after 72 hours of exposure to curcumin, the proliferation of MM cells alone or co-cultured was inhibited in a dose-dependent manner. Well. Well. I thought it was interesting that myeloma cells had to be exposed to curcumin for THREE days before anything happened…food for thought.
Another important finding: combined treatment with bortezomib and curcumin increased apoptosis in U266 cells as compared with either compound alone.
In the Discussion part of the study, the researchers inform us that cell viability of the IL-6 dependent cell line, U266, was enhanced by BMSCs, indicating that survival of U266 cells was considerably influenced by the interaction with BMSCs, most likely due to the release by BMSCs of several growth factors that promote MM cell growth. Curcumin inhibited the release of these growth factors, thus stunting myeloma cell growth. Good!
An important excerpt: […] synergism between curcumin and bortezomib can be achieved at low concentrations of bortezomib […]. So curcumin can potentiate the therapeutic efficacy of low dose bortezomib, thus reducing toxicity issues associated with the use of high-dose bortezomib. How about THAT? Wouldn’t it be great if myeloma patients could use lower doses of Velcade thanks to curcumin?
The researchers go on to say that only curcumin dramatically blocked the phosphorylation of both STAT3 and Erk. Phosphorylation of STAT3 and Erk protects tumor cells from undergoing apoptosis when cancer cells are exposed to anti-cancer drugs. In a nutshell, bortezomib didn’t stop phosphorylation, a process that protects tumor cells from dying; curcumin DID, whereby increasing the anti-myeloma effectiveness of bortezomib.
The researchers end by stating that the combination of curcumin and bortezomib can be utilized as a novel MM treatment regimen. I had already read that curcumin can be used in combination with Velcade, but I hadn’t yet seen such strong proof. And how about the study’s suggestion that lower doses of bortezomib could be used by myeloma patients if curcumin were added to the mix? Wowie zowie.