Ferroptosis induced by ferrous ions(Fe^(2+))and lipid peroxidation accumulation is a novel form of regulated cell death that has become a hot topic in tumor therapy research.Identifying small-molecule drugs that can i...Ferroptosis induced by ferrous ions(Fe^(2+))and lipid peroxidation accumulation is a novel form of regulated cell death that has become a hot topic in tumor therapy research.Identifying small-molecule drugs that can induce ferroptosis in tumor cells is a very attractive therapeutic strategy.Here,we screened a natural product,acevaltrate(ACE),which rapidly and strongly induces ferroptosis in colorectal cancer cells.ACE not only increases Fe^(2+)levels in colorectal cancer cells by targeting iron chaperones PCBP1/2 and reducing their expression but also disrupts the antioxidant system of colorectal cancer cells by targeting GPX4 and inhibiting its enzymatic activity,leading to its ubiquitin-mediated degradation.展开更多
基金funded by the National Natural Science Foundation of China(No.82374086,82141203,82104459,82430116)National Key Research and Development Program of China(2022YFC3502000)+5 种基金hanghai Municipal Science and Technology Major Project(ZD2021CY001)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTDD-202004)Science and Technology Commission of Shanghai Municipality(20YF1458700)Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(2023YZZ02)CAMS Innovation Fund for Medical Sciences(CIFMS)(2023-I2M-3-009)Key Project at Central Government Level:The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(2060302-2305-02)。
文摘Ferroptosis induced by ferrous ions(Fe^(2+))and lipid peroxidation accumulation is a novel form of regulated cell death that has become a hot topic in tumor therapy research.Identifying small-molecule drugs that can induce ferroptosis in tumor cells is a very attractive therapeutic strategy.Here,we screened a natural product,acevaltrate(ACE),which rapidly and strongly induces ferroptosis in colorectal cancer cells.ACE not only increases Fe^(2+)levels in colorectal cancer cells by targeting iron chaperones PCBP1/2 and reducing their expression but also disrupts the antioxidant system of colorectal cancer cells by targeting GPX4 and inhibiting its enzymatic activity,leading to its ubiquitin-mediated degradation.
