Screening of NF-kappa B inhibitors having new core structure and application to aggressive cancer treatment

2016 Fiscal Year Final Research Report

• Project/Area Number: 26350975
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical biology
• Research Institution: Aichi Medical University
• Principal Investigator: Umezawa Kazuo 愛知医科大学, 医学部, 教授 (70114402)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: NF-kappa B / 分子デザイン / 天然物 / がん / 転移 / 炎症 / DHMEQ / desmal

Outline of Final Research Achievements

Metastasis inhibitors are expected as new chemotherapeutic agents with little side effects. We previously discovered DHMEQ as an NF-kappa B inhibitor. It shows various anti-inflammatory and anticancer activities in animal experiments, but it contains epoxide moiety that causes instability. In the present research, we designed and synthesized an epoxide-free DHMEQ analog called SEMBL. SEMBL inhibited NF-kappa B as DHMEQ. It also inhibited cellular migration and invasion in ovarian carcinoma cells more strongly than DHMEQ. Moreover, it was shown to be more stable than DHMEQ in aqueous solution (published in 2017). In one hand, we previously discovered a novel plant-derived flavonoid desmal. In the present research, dismal was found to inhibit NF-kappa B. It also inhibited cellular migration and invasion in ovarian carcinoma cells (published in 2016). These inhibitors will be useful for the mechanistic study of metastasis and for the development of new chemotherapeutic agents.

Free Research Field

生物化学