Comparison of diarsenic oxide and tetraarsenic oxide on anticancer effects: relation to the apoptosis molecular pathway.
As2O3 has been reported to induce apoptosis and inhibit the proliferation of various human cancer cells. We evaluated the ability of a novel arsenic compound, As4O6, along with As2O3 in vitro and in vivo. To examine the levels of apoptosis of HPV 16-positive SiHa cervical cancer cell, flow cytometry and Western blotting were employed at various time intervals after two arsenic compound treatments. Ingenuity Pathway Analysis (IPA) was applied to investigate the differential cell death pathway of As4O6 and As2O3. The results showed that As4O6 was more effective in suppressing SiHa cell growth in vitro and in vivo compared to As2O3. In addition, the cell cycle was arrested at the sub-G1 phase by As4O6. Western blot analysis showed that the proliferating cell nuclear antigen (PCNA) and Bcl-XL with sequence homology to Bcl-2 were significantly suppressed by As4O6. However, the apoptosis-related proteins such as p21 and Bax were overexpressed by As4O6. IPA suggested that there is a significant difference between As2O3- and As4O6-induced cell death pathways. Taken together, As4O6 has a specific cell death pathway and possesses more potent anti-tumor effects on human cervical cancer cells in vitro and in vivo.
Chang
Hong-Seok
HS
Department of Therapeutic Radiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Bae
Su-Mi
SM
Kim
Yong-Wan
YW
Kwak
Sun-Young
SY
Min
Hyun-Jin
HJ
Bae
Il-Ju
IJ
Lee
Young-Joo
YJ
Shin
Jong-Chul
JC
Kim
Chong-Kook
CK
Ahn
Woong-Shick
WS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D000077237:Arsenic Trioxide