2. Academic Validation
  3. TRIP13 Plays an Important Role in the Sensitivity of Leukemia Cell Response to Sulforaphane Therapy

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

  • ACS Omega. 2024 Jun 6;9(24):26628-26640. doi: 10.1021/acsomega.4c03450.
Lei Liu 1,  Baixue Liao 2,  Ruiling Fan 3,  Yanxia Liu 4,  Aoshuang Li 2,  Lüye Liu 1,  Yan Li 5,  Jing Li 6
Affiliations

Affiliations

  • 1 Medical Research Center, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
  • 2 College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China.
  • 3 School of Pharmacy, North Sichuan Medical College, Nanchong 637000, Sichuan, China.
  • 4 College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
  • 5 Department of General Surgery, The 77th Army Hospital, Leshan 614000, Sichuan, China.
  • 6 Department of Pharmacological Research Lab, The Beibei Affiliated Hospital of Chongqing Medical University, The Ninth People's Hospital of Chongqing, Chongqing 400799, China.
PMID: 38911763 DOI: 10.1021/acsomega.4c03450
Abstract

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.

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