title: Comparison of As(2)O(3) and As(4)O(6) in the detection of SiHa cervical cancer cell growth inhibition pathway.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Kim
authors.forename: Su Mi
authors.initials: SM
authors.lastname: Bae
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Joon Mo
authors.initials: JM
authors.lastname: Lee
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Namkoong
authors.forename: Insu P
authors.initials: IP
authors.lastname: Lee
authors.forename: Chong Kook
authors.initials: CK
authors.lastname: Kim
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
authors.forename: Yong-Wan
authors.initials: YW
authors.lastname: Kim
authors.forename: Woong Shick
authors.initials: WS
authors.lastname: Ahn