To investigate whether licorice extracts (LE) combined with iron death inducer Erastin can induce iron death of colorectal cancer cell DLD1 through dipeptidyl peptidase-4 (DPP4).

DLD1 cells were randomly divided into control group, L-LE group (50 μg·mL^-1 LE), H-LE group (100 μg·mL^-1 LE), H-LE+Erastin group (100 μg·mL^-1 LE+30 nmol·L^-1 Erastin) and H-LE+Erastin+Sita (DPP4 inhibitor) group (100 μg·mL^-1 LE+30 nmol·L^-1 Erastin+31.25 μg·mL^-1 Sita), with drug interventions for 24 h. Cell cloning assay and Edu-594 cell proliferation test were conducted to determine the cloning and proliferation abilities of the cells. ELISA assay was used to detect the Fe²⁺ content and DPP4 activity. Flow cytometry was used to detect reactive oxygen species(ROS) content. Western blotting was used to detect the expression of solute carrier family 7 member 11(SLC7A11) and arachidonate lipoxygenase 3(ALOXE3) proteins.

Compared with control group, the cell cloning number decreased while the ROS content increased in L-LE group, H-LE group and H-LE+Erastin group (P<0.05 or P<0.01); and the proliferation ability and Fe²⁺ content decreased, DPP4 activity and ALOXE3 protein expression increased, SLC7A11 protein expression decreased in H-LE and H-LE+Erastin groups (P<0.05 or P<0.01). Compared with H-LE+Erastin group, the addition of Sita significantly increased cell cloning, proliferation and SLC7A11 protein expression, while significantly decreased Fe²⁺ content, DPP4 activity, ROS content and ALOXE3 protein expression (P<0.01).

LE combined with Erastin can induce iron death of colorectal cancer (CRC) cell through DPP4.