An arsenical compound,
As2O3 has been reported to be effective for treating acute
leukemia and induce apoptosis in many different
tumor cell types. In this study we designed a novel arsenical compound,
As4O6, and compared its ability to induce cell growth inhibition as well as gene expression profiles along with
As2O3 in HPV16 infected SiHa
cervical cancer cells. Both
As2O3 and
As4O6 induced apoptosis in SiHa cells, as determined by
a DNA ladder formation.
As4O6 was more effective in suppressing the growth of SiHa cells in vitro, as compared to
As2O3. To further compare gene expression profiles between these two drugs, we used a 384
cDNA microarray system. The gene expression profiles were also classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes. In the case of
As2O3, 41 genes were up- or down-regulated at least 2-fold, as compared to non-treatment, whereas, 65 genes were up- or down-regulated by
As4O6 treatment. In particular, 27 genes were commonly regulated by both
arsenic compounds. The GO analysis also indicated that down-regulation of cell-regulatory functions, such as cell cycle,
protein kinase activity and DNA repair, induces an anti-
tumor effect. Taken together, these data support that
As4O6 could be more effective than
As2O3 in inhibiting the growth of HPV16 infected
cervical cancer cells. This appears to be mediated through a unique but overlapping regulatory mechanism(s), suggesting that the regulated genes and cellular processes could be used for a new potential
drug approach for treating
cervical cancer in clinical settings.