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

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.