Arsenic trioxide

Arsenic trioxide has a relatively complex mechanism of action that can be divided into three major aspects.

1. Molecular mechanism in acute promyelocytic leukemia (APL):

In APL, tumor cells carry the fusion protein PML-RARα, which is generated by the t(15;17) translocation. This fusion protein blocks granulocyte differentiation. Arsenic trioxide can directly bind to PML/PML-RARα-related structures, promote their degradation, restore the normal architecture of PML nuclear bodies, facilitate cellular differentiation, and activate apoptosis-related pathways.

2. Induction of apoptosis and oxidative stress:

Arsenic trioxide increases the generation of intracellular reactive oxygen species (ROS), disrupts the mitochondrial membrane potential, and subsequently activates apoptotic pathways involving caspase-3, caspase-9, and related mediators, ultimately leading to cell death.

3. Inhibition of tumor angiogenesis and cell cycle progression:

It reduces the expression of vascular endothelial growth factor (VEGF), thereby suppressing angiogenesis-related signaling. It can also arrest cancer cells in the G₁ or G₂/M phase of the cell cycle.