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 acti...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.展开更多
Curcumenol,an effective ingredient of Wenyujin,has been reported that exerted its antitumor potential in a few cancer types.However,the effect and molecular mechanism of curcumenol in lung cancer are largely unknown.H...Curcumenol,an effective ingredient of Wenyujin,has been reported that exerted its antitumor potential in a few cancer types.However,the effect and molecular mechanism of curcumenol in lung cancer are largely unknown.Here,we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells.Next,we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time.Subsequently,using RNA sequencing,we found that the long non-coding RNA H19(lncRNA H19)was significantly downregulated in lung cancer cells treated with curcumenol,when compared to untreated controls.Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol,while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment.Mechanistically,we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p,thereby enhanced the transcription activity of its endogenous target,ferritin heavy chain 1(FTH1),a marker of ferroptosis.In conclusion,our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis,and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death.Therefore,our findings will hopefully provide a valuable drug for treating lung cancer patients.展开更多
基金supported by the grants National Natural Science Foundation of China (Nos. 81874380 and 82022075, to Xinbing Sui81730108 and 81973635, to Tian Xie)+4 种基金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 DuanLQ21H160038, to Jiao Feng)Zhejiang Province Science and Technology Project of TCM (Nos. 2019ZZ016, to Xinbing Sui2020ZQ046, to Ruonan Zhang, China)。
文摘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.
基金This work was financially funded by the grants National Natural Science Foundation of China(No.81874380 and 82022075,to Xinbing Sui,81730108 and 81973635,to Tian Xie,82104207,to Xueni Sun)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(No.LR18H160001,to Xinbing Sui)+5 种基金the Science and Technology Development Fund,Macao SAR(No.130/2017/A3,0099/2018/A3 and 0098/2021/A2,to Qibiao Wu)Science and Technology Planning Project of Guangdong Province(2020B1212030008,to Qibiao Wu)Zhejiang Provincial Natural Science Foundation of China(No.LQ20H160013,Ting DuanLQ21H160038,to Jiao Feng)Zhejiang Province Science and Technology Project of TCM(No.2019ZZ016,to Xinbing Sui2021ZQ058,to Ruonan Zhang,China).
文摘Curcumenol,an effective ingredient of Wenyujin,has been reported that exerted its antitumor potential in a few cancer types.However,the effect and molecular mechanism of curcumenol in lung cancer are largely unknown.Here,we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells.Next,we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time.Subsequently,using RNA sequencing,we found that the long non-coding RNA H19(lncRNA H19)was significantly downregulated in lung cancer cells treated with curcumenol,when compared to untreated controls.Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol,while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment.Mechanistically,we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p,thereby enhanced the transcription activity of its endogenous target,ferritin heavy chain 1(FTH1),a marker of ferroptosis.In conclusion,our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis,and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death.Therefore,our findings will hopefully provide a valuable drug for treating lung cancer patients.
