Casticin induces ferroptosis in human osteosarcoma cells through Fe<SUP>2+</SUP> overload and ROS production mediated by HMOX1 and LC3-NCOA4
作者全名：Jiwa, Habu; Xie, Zhou; Qu, Xiao; Xu, Jingtao; Huang, Yanran; Huang, Xiongjie; Zhang, Jun; Wang, Nan; Li, Ningdao; Luo, Jinyong; Luo, Xiaoji
作者地址：[Jiwa, Habu; Xie, Zhou; Qu, Xiao; Xu, Jingtao; Huang, Yanran; Huang, Xiongjie; Zhang, Jun; Li, Ningdao; Luo, Xiaoji] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped, Chongqing 400016, Peoples R China; [Luo, Jinyong] Chongqing Med Univ, Key Lab Diagnost Med Designated, Chinese Minist Educ, Chongqing 400016, Peoples R China; [Wang, Nan] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 3, Chongqing 400016, Peoples R China
通信作者：Li, ND; Luo, JY; Luo, XJ (通讯作者)，1 Youyi Rd, Chongqing 400016, Peoples R China.
来源：BIOCHEMICAL PHARMACOLOGY
ESI学科分类：PHARMACOLOGY & TOXICOLOGY
WOS号：WOS:001258068500001
JCR分区：Q1
影响因子：5.3
年份：2024
卷号：226
期号：
开始页：
结束页：
文献类型：Article
关键词：Osteosarcoma; Casticin; Ferroptosis; HMOX1; LC3; NCOA4; Chemical compound studied in this article: Casticin, CAS RN: 479-91-4
摘要：Osteosarcoma is a primary solid bone malignancy, and surgery + chemotherapy is the most commonly used treatment. However, chemotherapeutic drugs can cause a range of side effects. Casticin, a polymethoxyflavonoid, has anti-tumor therapeutic effects. This study is aim to investigate the anti-osteosarcoma activity of casticin and explore the mechanism. Crystal violet staining, MTT assay, colony formation assay, wound healing assay, transwell assay, hoechst 33,258 staining, and flow cytometry analysis were used to investigate the effects of casticin on proliferation, migration, invasion, and apoptosis of osteosarcoma cells in vitro. The intracellular Fe 2 + , ROS, MDA, GSH/GSSG content changes were detected using the corresponding assay kits. The mRNA sequencing + bioinformatics analysis and western blot were used to detect the possible mechanism. We found that casticin caused G2/M phase cell cycle arrest in human osteosarcoma cells, inhibited the migration and invasion, and induced cell apoptosis and ferroptosis. Mechanistic studies showed the ferroptosis pathway was enriched stronger than apoptosis. Casticin up-regulated the expression of HMOX1, LC3 and NCOA4, meanwhile it activated MAPK signaling pathways. Animal experiments proved that casticin also inhibited the growth and metastasis of osteosarcoma cell xenograft tumor in vivo. In conclusion, casticin can induce ferroptosis in osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. This provides a new strategy for osteosarcoma treatment.
基金机构：National Natural Science Foun-dation of China [81873998]; Chongqing Young and Middle-aged Medical High-end Talent Project [2019GDRC001]; Chongqing Talent Innovation and Entrepreneurship Leader Project [cstc2022ycjh-bgzxm0103]; Chongqing Technology Innovation and Application Development Special Key Project [cstb2021tiad-kpx0060]; Program for Youth Innovation in Future Medicine of Chongqing Medical University [W0086]
基金资助正文：<B>Funding information</B> This research was supported by the National Natural Science Foun-dation of China (No. 81873998) , Chongqing Young and Middle-aged Medical High-end Talent Project (No. 2019GDRC001) , Chongqing Talent Innovation and Entrepreneurship Leader Project (No. cstc2022ycjh-bgzxm0103) , Chongqing Technology Innovation and Application Development Special Key Project (No. cstb2021tiad-kpx0060) , and the Program for Youth Innovation in Future Medicine of Chongqing Medical University (No. W0086) .
