"Theaflavin-3,3' -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts"

作者全名："He, Tao; Lin, Xiaohong; Yang, Chaohua; Chen, Zhiyu; Wang, Linbang; Li, Qiaochu; Ma, Jingjin; Zhan, Fangbiao; Wang, Yang; Yan, Jin; Quan, Zhengxue"

作者地址："[He, Tao; Yang, Chaohua; Chen, Zhiyu; Wang, Linbang; Li, Qiaochu; Ma, Jingjin; Wang, Yang; Quan, Zhengxue] Chongqing Med Univ, Chongqing 400016, Peoples R China; [He, Tao; Yang, Chaohua; Chen, Zhiyu; Wang, Linbang; Li, Qiaochu; Ma, Jingjin; Wang, Yang; Quan, Zhengxue] Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [He, Tao; Yang, Chaohua; Chen, Zhiyu; Wang, Linbang; Li, Qiaochu; Ma, Jingjin; Wang, Yang; Quan, Zhengxue] Chongqing Med Univ, Orthoped Lab, Chongqing 400016, Peoples R China; [He, Tao] Chongqing Gen Hosp, Dept Orthopaed Trauma, Chongqing 401147, Peoples R China; [Lin, Xiaohong] Chongqing Gen Hosp, Dept Ultrasound, Chongqing 401147, Peoples R China; [Zhan, Fangbiao] Chongqing Univ, Dept Orthoped, Gorges Hosp 3, Wanzhou 404000, Chongqing, Peoples R China; [Yan, Jin] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Quan, ZX (通讯作者)，Chongqing Med Univ, Chongqing 400016, Peoples R China.; Quan, ZX (通讯作者)，Chongqing Med Univ, Dept Orthoped, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Quan, ZX (通讯作者)，Chongqing Med Univ, Orthoped Lab, Chongqing 400016, Peoples R China."

来源：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000880433700003

JCR分区：Q2

影响因子：7.31

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3 '-digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models."

基金机构：National Natural Science Foundation of China; Chongqing Yingcai Plan Project; Foundation of Chongqing University Three Gorges Hospital; General Project of Chongqing Natural Science Foundation; [82072976]; [cstc2021ycjh-bgzxm0041]; [2022YJKYXM- 001]; [2022YJKYXM- 043]; [cstc2021jcyj-msxmX0909]

基金资助正文："AcknowledgmentsThis work was supported in part by the National Natural Science Foundation of China (82072976), the Chongqing Yingcai Plan Project (No. cstc2021ycjh-bgzxm0041) (to ZXQ), the Foundation of Chongqing University Three Gorges Hospital (2022YJKYXM- 001 and 2022YJKYXM- 043), and the General Project of Chongqing Natural Science Foundation (cstc2021jcyj-msxmX0909). We also thank Dr. Jianxiao Li, Dr. Zhenglin Zhu, Dr. Yanran Huang, and Dr. Rui Yang (Chongqing Medical University)."