6 research outputs found
Theracurmin inhibits intestinal polyp development in Apcâmutant mice by inhibiting inflammationârelated factors
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Therefore, it is important to establish useful methods for preventing CRC. One prevention strategy involves the use of cancer chemopreventive agents, including functional foods. We focused on the wellâknown cancer chemopreventive agent curcumin, which is derived from turmeric. However, curcumin has the disadvantage of being poorly soluble in water due to its high hydrophobicity. To overcome this problem, the formation of submicron particles with surface controlled technology has been applied to curcumin to give it remarkably improved water solubility, and this derived compound is named Theracurmin. To date, the preventive effects of Theracurmin on hereditary intestinal carcinogenesis have not been elucidated. Thus, we used Apcâmutant mice, a model of familial adenomatous polyposis, to evaluate the effects of Theracurmin. First, we showed that treatment with 10â20 ”M Theracurmin for 24 hours reduced nuclear factorâÎșB (NFâÎșB) transcriptional activity in human colon cancer DLDâ1 and HCT116 cells. However, treatment with curcumin mixed in water did not change the NFâÎșB promoter transcriptional activity. As NFâÎșB is a regulator of inflammationârelated factors, we next investigated the downstream targets of NFâÎșB: monocyte chemoattractant proteinâ1 (MCPâ1) and interleukin (IL)â6. We found that treatment with 500 ppm Theracurmin for 8 weeks inhibited intestinal polyp development and suppressed MCPâ1 and ILâ6 mRNA expression levels in the parts of the intestine with polyps. This report provides a proof of concept for the ongoing Theracurmin human trial (JâCAPâC study)
The Radical Scavenger NZ-419 Suppresses Intestinal Polyp Development in Apc-Mutant Mice
Colorectal cancer is the fourth leading cause of cancer death worldwide, and it is important to establish effective methods for preventing colorectal cancer. One effective prevention strategy could be the use of antioxidants. However, the role of the direct antioxidative function of antioxidants against carcinogenesis has not been clarified. Thus, we aimed to determine whether the direct removal of reactive oxygen species by a hydroxyl radical scavenger, NZ-419, could inhibit colorectal carcinogenesis. NZ-419 is a creatinine metabolite that has been shown to be safe and to inhibit the progression of chronic kidney disease in rats, and it is now under clinical development. In the present study, we demonstrated that NZ-419 eliminated reactive oxygen species production in HCT116 cells after H2O2 stimulation and suppressed H2O2-induced Nrf2 promoter transcriptional activity. The administration of 500 ppm NZ-419 to Apc-mutant Min mice for 8 weeks resulted in a decrease in the number of polyps in the middle segment of the small intestine to 62.4% of the value in the untreated control (p < 0.05 vs. control group). As expected, NZ-419 treatment affected the levels of reactive carbonyl species, which are oxidative stress markers in the serum of Min mice. Suppression of the mRNA levels of the proliferation-associated factor c-Myc was observed in intestinal polyps of Min mice after NZ-419 treatment, with a weak suppression of epithelial cell proliferation assessed by proliferation cell nuclear antigen (PCNA) staining in the intestinal polyps. This study demonstrated that NZ-419 suppress the development of intestinal polyps in Min mice, suggesting the utility of radical scavenger/antioxidants as a cancer chemopreventive agent
Inhibition of NF-kappaB transcriptional activity enhances fucoxanthinol-induced apoptosis in colorectal cancer cells
Abstract Background Evidence from epidemiological and experimental studies has shown that the etiology of colorectal cancer (CRC) is related to lifestyle, mainly diet. At the same time, there are many foods and beverages that have been shown to provide protection against CRC. We turned our attention to a traditional Japanese food, brown algae, that contains carotenoids and various functional polyphenols, especially fucoxanthin (FX) and fucoxanthinol (FxOH). Results Both FX and FxOH treatments induced apoptosis in a dose-dependent and time-dependent manner as detected by annexin V / propidium iodide and the presence of a subG1 population in human colon cancer HCT116 cells. This apoptotic effect of FxOH was stronger than that of FX. We also found that nuclear factor-kappa B (NF-ÎșB) transcriptional activity was significantly increased by treatment with â„5âÎŒM FxOH. Thus, we cotreated the cells with FxOH plus NF-ÎșB inhibitor, and the results demonstrated that this cotreatment strongly enhanced the induction of apoptosis compared with the effects of FxOH or NF-ÎșB inhibitor treatment alone and resulted in X-linked inhibitor of apoptosis (IAP) downregulation. Conclusions This study suggested that FxOH is a more potent apoptosis-inducing agent than FX and that its induction of apoptosis is enhanced by inhibiting NF-ÎșB transcriptional activity via suppression of IAP family genes