Figure 7.

Schematic model of the mechanism by which vitamin D protects normal tissues during cisplatin-based chemotherapy by inhibiting caspase-mediated GSDME cleavage. In normal tissue cells, cisplatin-based chemotherapy induces cellular caspase signals, promoting the production and maturation of caspase-3, which subsequently recognizes and cleaves GSDME into the N-terminus and C-terminus. The N-terminus binds to the cell membrane and forms pores connecting the inside and outside of the cell to trigger pyroptosis. Vitamin D inhibits cellular caspase activation and ultimately inhibits pyroptosis in normal tissues. Therefore, it protects normal tissues from chemotherapy drug destruction and reduces the associated side effects.