Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells.

Abstract

Arsenic trioxide (As2O3) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As2O3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As2O3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As2O3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As2O3 than HPV 16-positive CaSki and SiHa cells. After As2O3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As2O3 is a potential anticancer drug for cervical cancer.

• Authors: Hongtao Wang, Peng Gao, Jie Zheng
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 451 Issue 4 Pg. 556-61 (Sep 05 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 25117446 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Arsenicals
• E6 protein, Human papillomavirus type 16
• Oncogene Proteins, Viral
• Oxides
• Papillomavirus E7 Proteins
• Repressor Proteins
• Retinoblastoma Protein
• Transcription Factor AP-1
• Tumor Suppressor Protein p53
• Arsenic Trioxide

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Arsenic Trioxide
• Arsenicals (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• HeLa Cells
• Human papillomavirus 16 (genetics)
• Humans
• Oncogene Proteins, Viral (biosynthesis, genetics)
• Oxides (pharmacology)
• Papillomavirus E7 Proteins (biosynthesis, genetics)
• Papillomavirus Infections (genetics)
• Repressor Proteins (biosynthesis)
• Retinoblastoma Protein (genetics)
• Transcription Factor AP-1 (metabolism)
• Tumor Suppressor Protein p53 (metabolism)
• Uterine Cervical Neoplasms (drug therapy, etiology, physiopathology)