Purpose: An arsenical compound, As(2)O(3), has been reported to be effective for treating acute leukemia and inducing apoptosis in many different tumor cells. In this study, the ability of As(4)O(6) to suppress cell growth and induce gene expression patterns was tested using a cDNA microarray in HPV16 immortalized cervical carcinoma cells, SiHa cells, along with As(2)O(3).
Materials and methods: A novel arsenical compound, As(4)O(6), was designed and its ability to induce cell growth inhibition as well as gene expression profiles along with As(2)O(3) in HPV16 infected SiHa cervical cancer cells was compared. Both As(2)O(3) and As(4)O(6) induced apoptosis in SiHa cells, as determined by DNA ladder formation. To further compare the gene expression profiles between these two drugs, a 384 cDNA microarray system was employed. Also, the gene expression profiles were classified into the Gene Ontology (GO) to investigate apoptosis-related cellular processes.
Results: As(4)O(6) was more effective i suppressing the growth of SiHa cells in vitro compared to As(2)O(3). In the case of treatment with As(2)O(3), 41 genes were up- or down-regulated at least 2 fold compared to non-treatment. However, 65 genes were up- or down-regulated by As(4)O(6) treatment. In particular, 27 genes were commonly regulated by both arsenic compounds. Also, the GO analysis indicated that down-regulation of cell-regulatory functions, such as cell cycle, protein kinase activity and DNA repair, induced anti-tumor effect.
Conclusion: These data support that As(4)O(6) could be more effective than As(2)O(3) 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 further used as a new potential drug approach for treating cervical cancer in clinical settings.
Keywords: Apoptosis; Arsenic compound; Cervical cancer; Gene ontology; cDNA microarray.