Arsenic compounds are a somewhat unique class of metals, which have been considered as both
carcinogens and chemotherapeutic agents for
cancers.
Tumor promotion effects of
arsenic are believed to be associated with its transactivational activities on
transcription factors, such as
AP-1 and NFkappaB, while the induction of cell apoptosis and differentiation by
arsenic is considered to be a mechanism for the chemotherapeutic effects of
arsenic. Here, we found that exposure of cells to
arsenite and
arsenate leads to transactivation of
retinoic acid response elements (RARE) and
glucocorticoid response elements (GRE) in mouse epidermal JB6 cells. These inductions occur in a time-dependent manner. Furthermore, induction of RARE activity by
arsenic was synergistically enhanced by co-treatment of cells with
retinoic acid, while GRE activation by
arsenic was not affected by combined treatment of cells with
fluocinolone acetonide (FA). In consideration of the important role of RARE and GRE in induction of cell differentiation, we speculate that transactivation of RARE and GRE by
arsenic may be involved in its induction of cell differentiation and anti-
cancer activities in addition to its induction of apoptosis.