Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review

Abstract

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. On the other hand, the process of cancer metastasis consists of cell detachment from the primary tumor, invasion, transportation by blood or lymphatic vessels, invasion, attachment, and formation of secondary tumor. Cell detachment from the primary tumor and subsequent invasion are considered to be early phases of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phases. The assay system for the latter phase was set up with intra-portal-vein injection of pancreatic cancer cells. Intraperitoneal administration of DHMEQ was found to inhibit liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also, when the pancreatic cancer cells treated with DHMEQ were inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis, since the 3D invasion just includes cell detachment and invasion into the matrix. DHMEQ inhibited the 3D invasion of breast cancer cells at 3D-nontoxic concentrations. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury

“…2c). TNF-α production (assessed by ELISA assay) by isolated CD11B + hepatic macrophages from CCl 4 -treated WT mice was reduced by the NF-κB inhibitors BAY11-7082 and DHMEQ 37 , or the ROS scavenger Nacetyl-L-cysteine (NAC) ( Fig. 2g).…”

Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View

“…One of these is certainly dehydroxymethylepoxyquinomicin (DHMEQ), which inhibits the nuclear translocation of NF-κB. Currently, there is a great deal of scientific evidence on the efficacy of DHMEQ in different types of neoplastic and even inflammatory diseases, in vitro and in vivo [120][121][122][123][124]. We tested DHMEQ, for the first time, on HCC cell lines (HA22T/VGH, HepG2, and HuH-6), in which the molecule produced cytotoxic and pro-apoptotic effects in a proportional manner to levels of constitutively activated NF-κB in the three cell lines.…”

NF‑κB inhibitor DHMEQ inhibits titanium dioxide nanoparticle‑induced interleukin‑1β production: Inhibition of the PM2.5‑induced inflammation model

“…It causes irreversible inhibition of NF-κB when added to the cultured cells (10), since it binds to the cysteine residue covalently (11). It was shown to ameliorate various animal models of inflammation and cancer without showing any side effect (12,13). Previously, it was shown to inhibit lipopolysaccharide (LPS)-induced inflammatory cytokine secretions in mouse monocyte leukemia RAW264.7 cells (14) and mouse primary culture macrophages (15).…”