DHMEQ was designed and synthesized by Japanese researchers based on the molecular structure of the antibiotic epoxyquinomicin C. According to a 2002 research report by these researchers shortly after DHMEQ was first developed: “DHMEQ inhibited the TNF-alpha-induced cellular DNA binding of nuclear NF-kappaB, but not the phosphorylation or degradation of I-kappaB. Moreover, DHMEQ inhibited the TNF-alpha-induced nuclear accumulation of p65, a component of NF-kappaB. On the other hand, DHMEQ did not inhibit the nuclear transport of Smad2 and the large T antigen. Also, it did not inhibit the TNF-alpha-induced activation of JNK, but synergistically induced apoptosis with TNF-alpha in human T cell leukemia Jurkat cells.” A 2005 report by some of the same researchers clarified the action of DHMEQ somewhat “In this cell line (MCF-7 cells), DHMEQ completely inhibited the tumor necrosis factor-alpha-induced activation of NF-kappaB. DHMEQ did not inhibit the degradation of IkappaB but inhibited the nuclear translocation of NF-kappaB by both p65/p50 and RelB/p52 pathways.” In other words, DHMEQ inhibits NF-kappaB expression by blocking its initial translocation from the cell cytoplasm into the cell nucleus rather than blocking its action on specific genes after it got into the nucleus. Summarizing some recent research:
* DHMEQ shows promise as a therapeutic agent against several forms of cancer, including multiple myeloma(ref), liver cancer(ref)(ref), human leukemia(ref)(ref), and bladder cancer(ref). It enhances the effect of taxanes as a therapy for thyroid cancer(ref). DHMEQ together with another NF-kappaB inhibitor bortezomib sensitises rituximab-resistant AIDS-B-non-Hodgkin lymphoma to apoptosis by various chemotherapeutic drugs(ref).
* DHMEQ may be effective as a therapeutic agent against several inflammatory diseases, including types 2 and 2 diabetes(ref).
* DHMEQ can suppresses growth and type I collagen accumulation in keloid fibroblasts(ref).
* DHMEQ suppresses osteoclastogenesis and expression in mouse arthritis(ref). “--suggesting the possibility of future application of NF-ÎºB inhibitors to rheumatoid arthritis therapy.” Osteoclasts are cells that breakdown bone tissues.
Summarizing, DHMEQ appears to show promise as a therapeutic agent for several conditions where over-expression of NF-kappaB is involved, recognizing that most of the studies to date have been on the cell and small-animal levels and not yet at the clinical level.
One interesting study published last month indicates a surprising no-no connected with potential uses of DHMEQ for anti-cancer purposes: it may be self-defeating to combine use of DHMEQ with a strong anti-oxidant. According to this study, in two human liver-cancer cell lines, DHMEQ kills the cancer cells by inducing reactive oxygen species (ROS, free radicals) in them. “DHMEQ stimulated reactive oxygen species (ROS) production in a dose-dependent manner, and that pre-treatment of the cells with the antioxidant N-acetyl-l-cysteine (NAC) significantly reduced DHMEQ-induced ROS generation. Accordingly, NAC completely reversed the DHMEQ-induced growth inhibition, caspases activation and cell death. DHMEQ-treated cells exhibited DNA damage, as evaluated by accumulation in nuclear foci of phospho-H2AX, which was completely reversed by NAC.”
In other words, the anti-oxidant NAC prevented the anti-cancer effects of DHMEQ. For those of us who are used to free radicals always being bad and anti-oxidants always being good there is an important message here. The opposite can be sometimes true if we are concerned with what goes on inside cancer cells. Also, the fact that most anti-oxidants are inhibitors of NF-kappaB can be consistent with at least one inhibitor of NF-kappaB (DHMEQ) being a pro-oxidant at least in some cancer cells. It is a wee bit mind-bending.