Comparison of effects of As2O3 and As4O6 on cell growth inhibition and gene expression profiles by cDNA microarray analysis in SiHa cells.
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.
Ahn
Woong Shick
WS
Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, Korea.
Bae
Su Mi
SM
Lee
Keun Ho
KH
Kim
Yong Wook
YW
Lee
Joon Mo
JM
Namkoong
Sung Eun
SE
Lee
Insu P
IP
Kim
Chong Kook
CK
Seo
Jeong-Sun
JS
Sin
Jeong-Im
JI
Kim
Yong-Wan
YW
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D015152:Blotting, Northern; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010087:Oxides / Q000627:therapeutic use*; D012313:RNA / Q000737:chemistry; D013997:Time Factors; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D001152:Arsenicals; D018076:DNA, Complementary; D010087:Oxides; D012313:RNA; D004247:DNA; D000077237:Arsenic Trioxide