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Artesunate induces G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis in A431 human epidermoid carcinoma cells
- Source :
- Anti-Cancer Drugs. 23:606-613
- Publication Year :
- 2012
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2012.
-
Abstract
- The anticancer effects of artesunate (ART) have been well documented. However, its potential against skin cancer has not been explored yet. Herein we reported that 60 μmol/l ART effectively inhibited A431 (human epidermoid carcinoma cells) growth but not that of HaCaT (normal human keratinocyte cells). Our results revealed that ART induced cell cycle arrest at G0/G1 phase through the downregulation of cyclin A1, cyclin B, cyclin D1, Cdk2, Cdk4, and Cdk6. This correlated with the upregulation of p21 and p27. The 5-bromodeoxyuridine incorporation assay also indicated that ART treatment reduced DNA synthesis in a time-dependent manner. Furthermore, ART induced mitochondrial apoptosis, as evidenced by annexin V/propidium iodide staining and western blot analysis. Interestingly, ART-induced apoptosis diminished under iron-deficient conditions but intensified under iron-overload conditions. Taken together, these findings demonstrated the potential of ART in treating skin cancer through the induction of G0/G1 cell cycle arrest and iron-mediated mitochondrial apoptosis and supported further investigations in other test systems.
- Subjects :
- Keratinocytes
Cancer Research
Cell cycle checkpoint
Iron
Cyclin B
Artesunate
Apoptosis
Cell Cycle Proteins
Resting Phase, Cell Cycle
chemistry.chemical_compound
Cyclin D1
Cell Line, Tumor
Humans
Pharmacology (medical)
Propidium iodide
Cell Proliferation
Pharmacology
biology
Caspase 3
Cell Cycle Checkpoints
Antineoplastic Agents, Phytogenic
G1 Phase Cell Cycle Checkpoints
Artemisinins
Mitochondria
HaCaT
Oncology
chemistry
Epidermoid carcinoma
Carcinoma, Squamous Cell
biology.protein
Cancer research
Cyclin A1
Subjects
Details
- ISSN :
- 09594973
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Anti-Cancer Drugs
- Accession number :
- edsair.doi.dedup.....533f506d2768d3c7415cf222b5f1a6e9