Fig. 5.

TGM2 functions as a target of kaempferol to induce pancreatic cancer cell apoptosis. a and b TGM2 protein and mRNA overexpression in PANC-1 and Mia PaCa-2 cells was confirmed by immunoblotting analysis and quantitative RT-PCR, respectively (***P < 0.001). The grouping of blots cropped from different parts of the same gel or from different gels, fields, or exposures was divided with white space. c Left, ROS alterations in TGM2-overexpressing PANC-1 and Mia PaCa-2 cells treated with kaempferol; right, quantification of ROS production in both TGM2-overexpressing pancreatic cancer cell lines, which is presented as the means ± SD (P < 0.0001 and P = 0.001, respectively). d and e Apoptotic rates of the TGM2-overexpressing and TGM2-scramble cell lines following kaempferol treatment (***P < 0.001). f Immunoblotting analysis of TGM2, NRF2, KEAP1, p-Akt, and p-mTOR levels in PANC-1 and Mia PaCa-2 cells overexpressing TGM2 following kaempferol treatment. The grouping of blots cropped from different parts of the same gel or from different gels, fields, or exposures was divided with white space. g A schematic illustrating the proposed ROS-associated mechanism by which kaempferol downregulates TGM2 expression to increase ROS levels and promote Akt/mTOR signaling inactivation, which contributes to the inhibition of cell proliferation and the induction of apoptosis