Back to Search
Start Over
PX-12-induced HeLa cell death is associated with oxidative stress and GSH depletion
- Source :
- Oncology Letters
- Publication Year :
- 2013
- Publisher :
- Spandidos Publications, 2013.
-
Abstract
- PX-12, as an inhibitor of thioredoxin (Trx), has antitumor activity. However, little is known about the toxicological effect of PX-12 on cervical cancer cells. In the present study, the growth inhibitory effects of PX-12 on HeLa cervical cancer cells in association with reactive oxygen species (ROS) and glutathione (GSH) levels were investigated. Based on MTT assays, PX-12 inhibited the growth of HeLa cells with an IC50 value of ~7 μM at 72 h. DNA flow cytometry analysis indicated that 5 and 10 μM PX-12 significantly induced a G2/M phase arrest of the cell cycle. PX-12 also increased the number of dead cells and annexin V-fluorescein isothiocyanate-positive cells, which was accompanied by the loss of mitochondrial membrane potential. All the investigated caspase inhibitors significantly rescued certain cells from PX-12-induced HeLa cell death. With respect to ROS and GSH levels, PX-12 increased ROS levels (including O2•−) in HeLa cells and induced GSH depletion. N-acetyl cysteine markedly reduced the levels of O2•− in PX-12-treated HeLa cells, and prevented apoptotic cell death and GSH depletion in these cells. By contrast, L-buthionine sulfoximine intensified cell death and GSH depletion in PX-12-treated HeLa cells. To conclude, this is the first study to demonstrate that PX-12 inhibits the growth of HeLa cells via G2/M phase arrest, as well as inhibiting apoptosis; the effect was associated with intracellular increases in ROS levels and GSH depletion.
- Subjects :
- reactive oxygen species
Cancer Research
Programmed cell death
PX-12
Cell
Articles
thioredoxin
Glutathione
Biology
Cell cycle
medicine.disease_cause
biology.organism_classification
HeLa
Cell biology
chemistry.chemical_compound
cell death
medicine.anatomical_structure
Oncology
chemistry
Apoptosis
medicine
Intracellular
Oxidative stress
Subjects
Details
- ISSN :
- 17921082 and 17921074
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Oncology Letters
- Accession number :
- edsair.doi.dedup.....28bd0466a3d30f4875c051cb3c204fad