Search and function elucidation of highly active natural products targeting cancer microenvironmental signals
Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
Date (from‐to) : 2017/04 -2020/03
Author : Ishibashi Masami
In this study, we examined screening programs using several kinds of luciferase cell-based assays mainly from natural products, with the aim of finding useful low-molecular compounds that act on cell signals that are enhanced in the cancer microenvironment. Screening studies were carried out targeting several intracellular signals involved in stem cell self-renewal and epigenetic gene transcription such as Wnt, Hedgehog, and Notch signals, cancer cell-selective apoptosis-inducing factors, and polycomb-constituting molecules. As a result, a number of useful bioactive natural products having Wnt signal inhibitory activity, TRAIL resistance overcoming activity, Bmi1 promoter inhibitory activity were isolated from our collection of plants and actinomycetes extracts, and their chemical structures were elucidated. We also investigated the mechanism of action of these active compounds through analyzing the effect on the expression of various proteins involved in cancer progression.