Potential new medicine - sulforaphane October 27, 2017 Source: Yaodu Sulfuraphane (1-Isothiocyanate-4-methanesulfonylbutane) (Sulforaphane), also known as "Lymesulfane", is an isothiocyanate, which is made from glucosinolates in plants. Obtained by hydrolysis of a myrosinase enzyme, which is a biologically active, electrophilic compound that can covalently modify proteins and other biomolecules. In the early 1900s, broccoli originated from the Brassica family, which was originally grown in California and is one of the most popular vegetables in the United States. From the second world war to the present, the United States is the world's largest exporter of broccoli. Broccoli is widely considered to be a healthy food rich in vitamins C, K, A, soluble fiber and many other nutrients. Interestingly, people have found effective anticancer activity in broccoli sprouts. The results of epidemiological related experiments show that it can detoxify carcinogens in the human body and reduce the incidence of cancer. For example, the extract of broccoli sprouts protects the experimenter from skin cancer due to UV radiation. Later, a large number of studies have shown that the high content of bioactive substance isothiocyanate in broccoli sprouts is also a powerful biological function of sulforaphane: it is likely to prevent prostate cancer; lyophilized broccoli is found in mouse experiments. The solution extract contains isothiocyanate to inhibit bladder cancer; antioxidant activity and cholesterol lowering and anti-obesity functions. Although there are widespread articles in the circle of friends about broccoli against cancer, what is the mechanism of sulforaphane anti-cancer? Researchers at the Life Science and Environmental Science Research and Development Center of Harbin University of Commerce have found that sulforaphane has an obvious effect on lung cancer, esophageal cancer and anterior gastric cancer after studying the anticancer mechanism of radish sulphate in broccoli (because of low radish flower yield). The mechanism of action is to induce the production of Phase II (carcinogenic factor detoxification) enzymes, and further act on the body's own anti-cancer system to regulate metabolism. Studies have found that the anti-cancer effect of sulforaphane plays a major role in blocking the carcinogenic effects of carcinogens, preventing carcinogens or their metabolites from entering target cells, while also eliminating carcinogens; inhibiting the division of cancer cells And growth, blocking the circulation pathway; promoting other protein secretion that kills cancer cells, blocking the role of carcinogens in inducing cancer. In addition, sulforaphane may play a role in the initiation of carcinogens, causing mutations in the early stages of cancer formation, and some inhibitory enzymes have dual cancer or tumor suppressor functions, degrading toxic substances, thereby resisting Cancer effect. At the same time, sulforaphane can also inhibit the production of Phase II enzyme, such as reducing the level of P450 enzyme or inhibiting its catalytic activity, thereby affecting the formation of active carcinogenic end products. By destroying the active centers of oncogenic factors or combining them with endogenous ligands, they are accelerated to be excreted, thereby acting as an anticancer. A few recent scientific articles related to sulforaphane have further unveiled its mystery. Cancer Letters Sulforaphane combined with paclitaxel Professor Zhang tao of the University of Michigan recently published an article on Cancer Letters, revealing the combined tumor suppressor mechanism of sulforaphane and paclitaxel. Taxanes such as paclitaxel or polyselenide paclitaxel are very common chemotherapeutic drugs for the treatment of breast cancer. However, the biggest problem with these chemotherapeutic drugs is that they are effective in killing differentiated cancer cells, and a side effect is an increase in differentiated cancer stem cells (phenotypic CSCs), thereby shortening the treatment interval and causing the disease to deteriorate. Sulforaphane is a natural product known to have strong anticancer activity, and its precursor glucosinolate is a very important secondary metabolite unique to cruciferous plants. In previous studies, it was found that sulforaphane is a good killer of cancer stem cells. So in this study, the authors hope to be able to treat cancer more effectively by combining a taxane-based chemotherapy drug with sulforaphane. The authors first verified in the breast cancer cell line that sulforaphane can indeed effectively inhibit the increase of NF-kB-mediated IL6 and IL8 expression caused by taxanes (this is considered to promote the differentiation of cancer stem cells). ). The authors then demonstrated in breast cancer cell lines and mouse models that the combination of these two natural products could better inhibit the growth of cancer cells over a long period of time. One of the most obvious phenotypes is a significant reduction in the probability of combined use of secondary tumors with polyselenide paclitaxel alone. Chemical Communication Looking for new targets for sulforaphane in cancer cells The sulforaphane, an isothiocyanate small molecule, prevents or inhibits the development of many cancers. It can covalently modify proteins and other biomolecules. It is widely believed that it can affect many targets and signaling pathways as pharmacological agents. However, its target and potential molecular mechanisms are not well understood. The authors aimed to identify targets for sulforaphane in two breast cancer cell lines using quantitative methods based on competitive chemical proteomics and to identify the relative affinities of these targets to sulforaphane. The authors designed and synthesized a new probe based on the alkynyl-labeled sulforaphane probe synthesized in the reported literature. The advantage of this probe is that the steric hindrance around the electrophilic warhead is greatly reduced, and the lipophilicity is very close to that of sulforaphane, which reduces the non-specific binding to some extent. Next, the authors used these two probes to treat the two breast cancer cells, MCF7 and MDA-MB-231, respectively, in an attempt to verify the biological activities of the two probes through competition experiments. Finally, the authors identified 129 and 121 high-confidence targets in MCF7 and MDA-MB-231 breast cancer cells, of which 56 were conserved targets. By analyzing the data, we found some important protein targets that regulate cell proliferation and apoptosis, such as NF-kb, STAT3, STK, etc., which are present in both breast cancer cell lines. These targets identified by chemical proteomics methods can help people better understand the mechanism of action of sulforaphane. Science Translational Medicine Sulforaphane and type 2 diabetes Professor Anders H. Rosengren of Lund University in Sweden found the association between sulforaphane and type 2 diabetes. The sulforaphane has a very good effect on diabetes. The authors found a pair of genes closely related to type 2 diabetes through the previously established method of studying the relationship between disease characteristics and drug characteristics. Under this method, the drug characteristics of sulforaphane are the most significant, which means that the drug has the most significant effect on disease characteristics. Therefore, the authors explored the effects of treating type 2 diabetes in the cell, mouse and patient layers. In the end, the authors found that sulforaphane reduced glucose production in rat hepatocytes and enhanced glucose tolerance in high-fat or high-sugar diets. Of the 97 type 2 diabetic volunteers, 3 did not use metformin, and the Others all took metformin. In addition, volunteers took high concentrations of sulforaphane or placebo daily for three months. In the end, three subjects were able to control blood glucose levels without metformin. Compared with the placebo group, the control group had a good blood sugar lowering effect even when taking metformin. Radish sulphate may be a potential drug for type 2 diabetes in addition to cancer in the future. Theriogenology Radish Sulfur and Antioxidant Mechanism and Apoptosis The sulforaphane can trigger a series of antioxidant enzymes by activating the Nrf2 signaling pathway at a specific concentration, which is likely to neutralize the oxidative stress induced by ROS. This article explores the potential concentrations of sulforaphane in the ovarian granulosa cells that cause antioxidant and apoptotic effects. Bovine ovarian granulosa cells were obtained from ovarian follicles prior to ovulation and cultured with different concentrations of sulforaphane (0-80 μM). Three concentrations were screened based on the phenotypic evaluation for further study: 2 μM (low ), 10 μM (middle) and 20 μM (height). The experimental results show that when the concentration of sulforaphane is greater than 15 μM, there is a high cytotoxic effect and the cell activity is greatly reduced. The expression of NRF2 was increased by 3-8 fold in ovarian spleen cells cultured with sulforaphane, but the expression of Kelch Like ECH Associated Protein 1 (KEAP1) was down-regulated or similar to the control group under the same treatment conditions. Compared with the control group, the downstream genes of NRF2 activation (PRDX1, CAT, TXN1 and SOD1) were also highly expressed 2-5 times. In addition, in the 20 μM SFN cultured cells, the level of ROS aggregation was higher and caused a high level of aggregation of fat droplets. Compared with the control group, the mitochondrial activity of the cells cultured with 2 and 10 μM sulforaphane was almost unchanged, and when the concentration was increased to 20 μM, the activity of mitochondria was greatly reduced. The results showed that 10μM sulforaphane could activate Nrf2 signaling pathway without causing apoptosis, which was beneficial to promote the production of phase II antioxidant enzyme. However, high concentrations of sulforaphane (20 μM) cause excessive ROS, leading to mitochondrial dysfunction, which triggers cell stress and ultimately triggers apoptosis. This article strongly demonstrates the concentration-dependent antioxidant and apoptotic effects of sulforaphane in ovarian granulosa cells. PLoS one Potential applications: combined with chemotherapy to improve anti-cancer efficacy The anticancer effect of sulforaphane in various cell lines has attracted widespread attention. It has been reported to have anti-malignant tumor proliferation and radiation sensitization properties in head tumors and cervical cancer, but combined with radish in pancreatic cancer. The role played by sulphur and after irradiation is still unclear. In the established four pancreatic cancer cell lines, after treatment with sulforaphane and radiation, the authors studied the survival of clones by flow cytometry and Western blotting, the distribution of cell cycle after cell lysis and comparison of DNA. damage. Both sulforaphane and radiation showed a strong dose-dependent survival reduction in the clone assay, induced G2/M cell cycle arrest and an increase in the expression of γH2AX protein, which indicates DNA damage. The treatment is more pronounced, and cell cycle disturbances and DNA damage last longer than a single treatment. Moreover, sulforaphane causes a decrease in DNA repair proteins Ku70, Ku80 and XRCC4. The article demonstrates that the combination of sulforaphane and radiation is more effective than single treatment in causing DNA damage and inhibiting growth. Radish tassels have great potential in improving the efficacy of chemotherapy. Interventional Accessories,Introducer Sheath,Introducer Sheath Kit,arterial sheath introducer Anesthesia Medical Co., Ltd. , https://www.honestymed.com