Mechanisms of Action

Arsenic causes cellular alterations via numerous pathways, including induction of apoptosis, inhibition of proliferation, stimulation of differentiation, and inhibition of angiogenesis20 (Figure 16.1). The fundamental biological effects of arsenic (mainly the trivalent forms, arsenite and As2O3) may be mediated by reactions with closely spaced cysteine residues on critical cell proteins.21 The subsequent anti-carcinogenic or carcinogenic actions of arsenic could be due to combined molecular mechanisms that are related to length of arsenic exposure (e.g. acute vs chronic), level of exposure (low vs high doses) and/or species of arsenic exposure (e.g. arsenite, arsenate, MMA, DMA, etc.). Mechanisms of the anti-cancer activities could also depend on the cell types.22 In recent years, when arsenic was reintroduced to the modern medicine for the treatment of APL, much attention has been focused on the mechanisms of action for this leukemia. In vitro and in vivo experiments suggested that induction of apoptosis and partial differentiation of APL cells are likely to constitute the cellular effects of As2O3. The induction of apoptosis and partial differentiation by arsenic are mediated via multiple and complex pathways.

As2O3

As2O3

*Guanosine Triphosphate

Figure 16.1 Mechanisms of action of As2O3 in the treatment of malignancies

*Guanosine Triphosphate

Figure 16.1 Mechanisms of action of As2O3 in the treatment of malignancies

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