Figure 10.

Schematic depiction of the mechanisms involved in H₂S-mediated tumor resistance to PX-12. H₂S increased tumor cell resistance to H₂S through multiple mechanisms: (1) H₂S promotes Trx in the reduced state, counteracting the thiol-inhibiting effect of PX-12; (2) H₂S directly reacts with PX-12, leading to the cleavage of disulfide bond in PX-12 and PX-12 deactivation; and (3) H₂S induces sulfhydryl residues in proteins that competes with Trx in binding PX-12, causing a reduced binding of PX-12 to Trx.