Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1  

作　　者：Na Kong Xiaying Chen Jiao Feng Ting Duan Shuiping Liu Xueni Sun Peng Chen Ting Pan Lili Yan Ting Jin Yu Xiang Quan Gao Chengyong Wen Weirui Ma Wencheng Liu Mingming Zhang Zuyi Yang Wengang Wang Ruonan Zhang Bi Chen Tian Xie Xinbing Sui Wei Tao 

机构地区：[1]College of Pharmacy and Department of Medical Oncology,the Affiliated Hospital of Hangzhou Normal University,School of Medicine,Hangzhou Normal University,Hangzhou 311121,China [2]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines,Engineering Laboratory of Development and Application of Traditional Chinese Medicines,Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province,Hangzhou Normal University,Hangzhou 311121,China [3]Center for Nanomedicine and Department of Anesthesiology,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA

出　　处：《Acta Pharmaceutica Sinica B》2021年第12期4045-4054,共10页药学学报（英文版）

基　　金：supported by the grants National Natural Science Foundation of China (Nos. 81874380 and 82022075, to Xinbing Sui;81730108 and 81973635, to Tian Xie);Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (No. LR18H160001, to Xinbing Sui);Zhejiang Provincial Natural Science Foundation of China (Nos. LQ20H160013, Ting Duan;LQ21H160038, to Jiao Feng);Zhejiang Province Science and Technology Project of TCM (Nos. 2019ZZ016, to Xinbing Sui;2020ZQ046, to Ruonan Zhang, China)。

摘　　要：Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.

关 键 词：BAICALIN Ferroptosis Bladder cancer FTH1 DEFEROXAMINE 

分 类 号：R285[医药卫生—中药学]