A friend (thank you!) sent me an MD Anderson study published in Blood (see abstract: http://tinyurl.com/2l4hb3) in July 2007. The study informs us that Salinosporamide A, a powerful proteasome inhibitor extracted from a marine bacterium, Salinispora tropica, also suppresses NF-kappa B, inhibits RANKL-induced osteoclastogenesis, and can overcome MM cell resistance to bortezomib (Velcade). The latter process, by the way, according to these researchers, would indicate that these two proteasome inhibitors have different mechanisms of action; therefore, when administered together, their effect would be synergistically stronger. Salinosporamide A also enhances the cytotoxicity of thalidomide, and inhibits the expression of the infamous COX-2 mentioned in previous posts. Among other things.
This extract, which was renamed NPI-0052, is currently being tested in a Phase I clinical trial for relapsed and relapsed/refractory MM patients in various locations throughout the U.S. (see: http://tinyurl.com/2klq9c) The April 2007 press release informing of the clinical trial can be read here: http://tinyurl.com/3832rf
In 2005, the Dana-Farber Cancer Institute published a study (abstract: http://tinyurl.com/2odmp4; full study: http://tinyurl.com/2qo9aj), which examines the synergism of the combination bortezomib- NPI-0052. However, since this particular study is available online, I won’t add anything else, but urge those interested to go have a look.
Back to the 2007 MD Anderson study. Researchers found that NPI-0052 was a more potent proteasome inhibitor than bortezomib but, they caution, this does not necessarily mean that it will be more effective than Velcade in clinical testing. The study ends: Overall, this study showed for the first time that the antiproliferative, proapoptotic, anti-osteoclastogenic, and anti-invasive effects of NPI-0052 might be mediated through the suppression of NF-kB and NF-kB-regulated gene products. Together, these findings provide a novel opportunity to exploit NPI-0052 proteasome inhibitor, not only in the treatment of cancer through the modulation of NF-kB activation pathway. Thus, use of NPI-0052 might provide a novel approach to the treatment of myeloid leukemia and potentially other types of cancers that are resistant of chemotherapy and radiotherapy. This study also informs us that NPI-0052 was first discovered during the fermentation of Salinispora tropica, a new seawater-requiring actinomycete found in marine sediments in the Bahamas.
How about that? An extract from a bacterium living in ocean sediment can induce apoptosis of multiple myeloma cells, colon cancer cells, chronic lymphocytic leukemia, acute lymphocytic leukemia and acute myeloid leukaemia. And I have written at least one post against…bacteria (well, germs!)! I (almost) stand corrected! 