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Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPK & alpha;/SLC7A11/GPX4 axis in colorectal cancer

文献类型：期刊论文

作者Ma, Xiaoqi1; Xu, Midie2,3,4; Zhang, Xing1; Wang, Xin2; Su, Kexin1; Xu, Zihang5; Wang, Xiaoyu1,6; Yang, Yifu1
刊名CELL BIOLOGY INTERNATIONAL
出版日期2023-07-20
页码12
关键词endoplasmic reticulum stress intracellular ferrous iron miRNA
ISSN号1065-6995
DOI10.1002/cbin.12072
通讯作者Wang, Xiaoyu(0000002733@shutcm.edu.cn) ; Yang, Yifu(0000002402@shutcm.edu.cn)
英文摘要The present study aims to investigate the mechanism of the nature compound gambogenic acid (GNA) on the apoptosis and ferroptosis in colorectal cancer (CRC). The effect of GNA on the proliferation of CRC cell lines were detected by MTT and clonogenic assay. The xenograft tumor model was established, and the inhibition effect of GNA were evaluated by observing the tumor growth. The endoplasmic reticulum (ER) of HCT116 was observed by using the ER tracker. The TargrtScan database was used to predict the miRNA binding sites. The level of miRNA with GNA treatment was explored by real-time quantitative PCR. The effect of ferroptosis were evaluated by detect the expression of reactive oxygen species (ROS), intracellular ferrous iron (Fe2+), malondialdehyde (MDA), glutathione (GSH), subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase (GPX)4, transferrin, and ferritin by Western blot. GNA isolated from gamboge can inhibit the growth and proliferation of CRC cell lines in a concentration-dependent manner. GNA activated ER stress by upregulating miR-1291, and miR-1291 targeted the forkhead box protein A2 (FOXA2). GNA also induced ROS production and mediated the Fenton reaction by activating transferrin to increase Fe2+, thus inducing ferroptosis. In addition, GNA could induce ferroptosis through the depletion of GSH and GPX4. Furthermore, GNA treatment regulated iron metabolism by activating AMPK & alpha;/SLC7A11/GPX4 signaling. In conclusion, GNA activated ER stress via miR-1291 and induced ferroptosis in CRC cells and might be a new inducer of ferroptosis, which can expand the efficacy of chemotherapy drugs.
WOS关键词ACTIVATION ; AUTOPHAGY
资助项目National Natural Science Foundation of China[82273370] ; National Natural Science Foundation of China[82274229] ; Clinical Research Project of Shanghai Shenkang Hospital Development Center[SIMM2205KF-16] ; State Key Laboratory of Drug Research[SHDC2020CR4068] ; State Key Laboratory of Drug Research[SHWSRS (2020) 087] ; State Key Laboratory of Drug Research[SIMM2205KF-16] ; Young Xinglin Scholar of Shanghai University of Traditional Chinese Medicine[A2-X200050316] ; Shanghai Science and Technology Plan Project[21DZ2271000] ; Natural Science Foundation of Shanghai[22ZR1413000] ; Clinical Research Project of Shanghai Shenkang Hospital Development Center[SHDC2020CR4068] ; Shanghai Rising Stars of Medical Talents Youth Development Program Youth Medical Talents-Specialist Program[SHWSRS (2020) 087]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:001032340500001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/306704]  
专题新药研究国家重点实验室
通讯作者Wang, Xiaoyu; Yang, Yifu
作者单位1.Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China
2.Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China
3.Fudan Univ, Shanghai Med Coll, Dept Med Oncol, Shanghai, Peoples R China
4.Fudan Univ, Inst Pathol, Shanghai, Peoples R China
5.Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Xiaoqi,Xu, Midie,Zhang, Xing,et al. Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPK & alpha;/SLC7A11/GPX4 axis in colorectal cancer[J]. CELL BIOLOGY INTERNATIONAL,2023:12.
APA Ma, Xiaoqi.,Xu, Midie.,Zhang, Xing.,Wang, Xin.,Su, Kexin.,...&Yang, Yifu.(2023).Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPK & alpha;/SLC7A11/GPX4 axis in colorectal cancer.CELL BIOLOGY INTERNATIONAL,12.
MLA Ma, Xiaoqi,et al."Gambogenic acid inhibits proliferation and ferroptosis by targeting the miR-1291/FOXA2 and AMPK & alpha;/SLC7A11/GPX4 axis in colorectal cancer".CELL BIOLOGY INTERNATIONAL (2023):12.

入库方式： OAI收割

来源：上海药物研究所

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