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TRIP13 Plays an Important Role in the Sensitivity of Leukemia Cell Response to Sulforaphane Therapy
Lei Liu1, Baixue Liao2, Ruiling Fan3
1Medical 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.
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.
Insights
Sulforaphane inhibits acute myeloid leukemia (AML) growth by targeting TRIP13. Inhibiting TRIP13 with DCZ0415 blocks sulforaphane
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sulforaphane, a cruciferous vegetable compound, exhibits anticancer properties, particularly against leukemia.
- The precise molecular mechanisms underlying sulforaphane's growth inhibition in acute myeloid leukemia (AML) remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular targets of sulforaphane in AML cells.
- To identify novel therapeutic strategies for AML treatment by investigating sulforaphane's mechanism of action.
Main Methods:
- Proteomic analysis of U937 AML cell line treated with sulforaphane.
- Key driver analysis of the leukemia network to identify regulatory factors.
- In vitro and in vivo experiments using TRIP13 inhibitor DCZ0415 to assess its impact on sulforaphane's effects.
Main Results:
- Proteomic analysis identified TRIP13 as a key regulatory factor in sulforaphane-induced growth inhibition.
- DCZ0415 pretreatment attenuated sulforaphane-induced apoptosis and cell cycle arrest via the PI3K/Akt/mTOR pathway.
- DCZ0415 pretreatment reduced sulforaphane's inhibitory effect on tumor volume in vivo.
Conclusions:
- TRIP13 is crucial for leukemia cell sensitivity to sulforaphane.
- This study reveals TRIP13 as a potential therapeutic target for AML.
- Findings enhance understanding of sulforaphane's antileukemic mechanisms.
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