GSDME and cancer: For instance, triptolide treatment inhibits the expression of mitochondrial hexokinase and c-Myc II in cancer cells, activating the BAD/BAX caspase-3 cascade and ultimately leading to GSDME-dependent pyroptosis.355 Another small compound, gambogic acid, can also induce caspase-3/GSDME pyroptosis, simultaneously enhancing cancer immunotherapy.356 Miltirone, a natural substance with anticancer activity, simultaneously prompts the proteolytic cleavage of GSDME and caspase-3, thereby inhibiting the viability of HepG2 or Hepa1-6 cells.