Endoplasmic reticulum stress is involved in hydrogen peroxide induced apoptosis in immortalized and malignant human oral keratinocytes.

摘要: Background Although hydrogen peroxide may play an important role in the development of cancer, it can be efficient inducer apoptosis cancer cells; exact mechanism by which this action occurs is not completely understood oral cells. Method In study, mechanisms H(2)O(2) inhibited growth and induced were differentially investigated using HPV-immortalized human keratinocytes (IHOK) cells (HN4). Results treatment sensitively dose-dependently inhibition typical IHOK HN4 cells, as demonstrated a decreased level cell viability, increased population sub-G(0)/G(1) phase, ladder formation genomic DNA, chromatin condensation accumulation Annexin V(+)/PI(+) Furthermore, expression Bax, p53 p21(WAF1/CIP1) increased, whereas Bcl-2 immortalized malignant that treated with H(2)O(2). addition, cytochrome-c from mitochondria was observed H(2)O(2)-treated accompanied activation caspase-3 -9. Additionally, upregulation CHOP, GRP78 several representative endoplasmic reticulum (ER) stress-responsive proteins, including heme oxygenase-1. Conclusion Overall, these results suggest triggers via mitochondrial ER stress pathway increasing cellular levels sufficiently lead to selective killing therefore therapeutically useful.