TRIP13 Plays an Important Role in the Sensitivity of Leukemia Cell Response to Sulforaphane Therapy

作者全名：Liu, Lei; Liao, Baixue; Fan, Ruiling; Liu, Yanxia; Li, Aoshuang; Liu, Lu''ye; Li, Yan; Li, Jing

作者地址：[Liu, Lei; Liu, Lu''ye] Southwest Jiaotong Univ, Affiliated Hosp, Peoples Hosp Chengdu 3, Med Res Ctr,Coll Med, Chengdu 610031, Sichuan, Peoples R China; [Liao, Baixue; Li, Aoshuang] Southwest Jiaotong Univ, Coll Med, Chengdu 610031, Sichuan, Peoples R China; [Fan, Ruiling] North Sichuan Med Coll, Sch Pharm, Nanchong 637000, Sichuan, Peoples R China; [Liu, Yanxia] Third Mil Med Univ, Army Med Univ, Coll Pharm, Chongqing 400038, Peoples R China; [Li, Yan] 77th Army Hosp, Dept Gen Surg, Leshan 614000, Sichuan, Peoples R China; [Li, Jing] Chongqing Med Univ, Beibei Affiliated Hosp, Peoples Hosp Chongqing 9, Dept Pharmacol Res Lab, Chongqing 400016, Peoples R China

通信作者：Li, Y (通讯作者)，77th Army Hosp, Dept Gen Surg, Leshan 614000, Sichuan, Peoples R China.; Li, J (通讯作者)，Chongqing Med Univ, Beibei Affiliated Hosp, Peoples Hosp Chongqing 9, Dept Pharmacol Res Lab, Chongqing 400016, Peoples R China.

来源：ACS OMEGA

ESI学科分类：CHEMISTRY

WOS号：WOS:001242837400001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：9

期号：24

开始页：26628

结束页：26640

文献类型：Article

关键词：　

摘要：Sulforaphane is one of the most characterized isothiocyanate compounds in cruciferous vegetables and shows anticancer effects, especially antileukemia properties. However, the molecular mechanism of the growth inhibition effect of sulforaphane in acute myeloid leukemia (AML) has not been fully explored. In the present study, a proteomic analysis was performed on the AML cell line U937 responding to sulforaphane treatment to identify novel and efficient therapeutic targets of sulforaphane on AML cells. Key driver analysis was run on the leukemia network, and TRIP13 was identified as a key regulatory factor in sulforaphane-induced growth inhibition in U937 cells. Pretreatment with DCZ0415, an inhibitor of TRIP13, could significantly attenuate sulforaphane-induced cell apoptosis and cell cycle arrest in vitro through the PI3K/Akt/mTOR signaling pathway. In addition, the inhibitory effect of sulforaphane on the tumor volume could also be obviously attenuated by the pretreatment of DCZ0415 in vivo. These results indicate that TRIP13 plays an important role in the sensitivity of leukemia cell response to sulforaphane treatment, and these findings expand the understanding of the mechanism of the antileukemic effect of sulforaphane and provide a new target for the treatment of AML.

基金机构：Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0175]; Third People's Hospital of Chengdu Scientific Research Project [2023PI19]

基金资助正文：This work was supported by grants from The Chongqing Natural Science Foundation (cstc2021jcyj-msxmX0175) and The Third People's Hospital of Chengdu Scientific Research Project (2023PI19).