Abstract | OBJECTIVES: Human papillomavirus (HPV) is directly associated with the occurrence and development of cervical cancer. Targeting HPV infection has become the priority in treatment and prevention. Some treatment strategies have shown a limited therapeutic potential in suppressing and reversing the oncogenic effects of HPVs, but are compromised by the toxicity, immune suppression and the expense. Arsenic trioxide ( As2O3) has shown therapeutic efficacy in the treatment of haematological and solid cancer and has been demonstrated to effectively induce apoptosis of HPV-infected cervical cancer cells in vitro. Here, we examined the effects and possible molecular pathway of As2O3-induced apoptosis in HPV-infected and noninfected cervical cancer cells. METHODS:
As2O3 was added to HPV-infected cell lines HeLa and CaSki and the HPV-negative cell line C33A at concentrations from 1 to 10 µmol/l. Cell proliferation rates were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after exposure. Expressions of tumour suppressor gene p53, activated caspase-3 and cell cycle distribution were evaluated in relation to HPV-E6 protein expression by confocal microscopy immunofluorescent staining and flow cytometry. RESULTS:
As2O3 reduced cell populations by 16% in C33A but by 48-60% in HPV-infected cell lines CaSki and HeLa. The expression of HPV-E6 proteins was drastically down-regulated in a dose-dependent manner, whereas p53 and activated caspase-3 expressions increased in the HPV-infected cell lines. Flow cytometry demonstrated cell cycle arrest in S-G2/M phases, and increasing apoptotic bodies were seen in HPV-infected lines only. CONCLUSION:
As2O3, at low concentrations, inhibited HPV-E6 protein expression, leading to up-regulated p53 levels, induced S to G2/M arrest and apoptosis.
|
Authors | Xuesong Wen, Dong Li, Yunyan Zhang, Shiping Liu, Lucy Ghali, Ray K Iles |
Journal | Anti-cancer drugs
(Anticancer Drugs)
Vol. 23
Issue 3
Pg. 280-7
(Mar 2012)
ISSN: 1473-5741 [Electronic] England |
PMID | 22245994
(Publication Type: Journal Article)
|
Chemical References |
- Antineoplastic Agents
- Arsenicals
- E6 protein, Human papillomavirus type 16
- Oncogene Proteins, Viral
- Oxides
- Repressor Proteins
- Tumor Suppressor Protein p53
- Caspase 3
- Arsenic Trioxide
|
Topics |
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Arsenic Trioxide
- Arsenicals
(pharmacology)
- Caspase 3
(metabolism)
- Cell Line, Tumor
(virology)
- Dose-Response Relationship, Drug
- Female
- HeLa Cells
(drug effects, virology)
- Humans
- Oncogene Proteins, Viral
(metabolism)
- Oxides
(pharmacology)
- Papillomavirus Infections
(drug therapy, metabolism, pathology)
- Repressor Proteins
(metabolism)
- Tumor Suppressor Protein p53
(metabolism)
- Uterine Cervical Neoplasms
(drug therapy, metabolism, pathology, virology)
|