Abstract
BackgroundWe are attempting to elucidate the mechanism of apoptotic cell death induced by hypoxia in oral cancer cells. Since hypoxia can render solid tumors more resistant to radiation and chemotherapy, understanding the pathways involved in hypoxia-induced apoptosis of oral cancer cells would be of significant therapeutic value.ResultsHere we showed that oral cancer cells from primary tumor and lymph node metastasis undergo apoptosis after 24 to 48 h of hypoxia. During hypoxic growth, an increase in caspase-3 proteolytic activity was observed, accompanied by the cleavage of PARP (poly (ADP-ribose) polymerase) indicative of caspase activity. In addition, hypoxic stress also lead to activation of caspase-8, -9, and -10 but not -1, elicited the release of cytochrome C into the cytosol, and resulted in internucleosomal DNA fragmentation.ConclusionThese results show that hypoxia-induced apoptosis in oral carcinoma cell lines relies on both intrinsic (mitochondrial) and extrinsic (cell death receptor mediated) pathways. This novel evidence will assist in designing more efficient combination chemotherapy approaches as promising strategy for the treatment of oral cancers.
Highlights
We are attempting to elucidate the mechanism of apoptotic cell death induced by hypoxia in oral cancer cells
We observed that hypoxia-induced apoptotic cell death occurs through activation of caspase 8, and cytochrome C release, caspase-9 activation, and results in caspase 3 processing, PARP cleavage, and DNA fragmentation. These results suggest that hypoxia-induced apoptosis in oral carcinomas cells relies on both intrinsic and extrinsic pathways
Since we observed that hypoxia activated caspase-3 in the oral carcinoma cells, we investigated the cleavage of the caspase-3 substrate PARP under hypoxic versus normal growth
Summary
We are attempting to elucidate the mechanism of apoptotic cell death induced by hypoxia in oral cancer cells. Since hypoxia can render solid tumors more resistant to radiation and chemotherapy, understanding the pathways involved in hypoxia-induced apoptosis of oral cancer cells would be of significant therapeutic value. A reduction in the level of tissue oxygen tension, occurs during acute and chronic vascular disease, pulmonary disease and cancer, and can lead to apoptotic or necrotic cell death [3,4]. Fast growing tumors become hypoxic because newly developed blood vessels are inefficient and have poor blood flow. Hypoxic growth can result in a tumor with more aggressive growth characteristics and more malignant (page number not for citation purposes)
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