Aspirin-induced apoptosis in human gastric cancer epithelial cells: relationship with protein kinase C signaling.
This study examined the relationship of protein kinase C (PKC) signaling with apoptosis induced by aspirin (ASA) in gastric surface cancer cells (AGS cell line). We found increased expression of two PKC isoforms (alpha and betaII) that translocated from the cytosol into the cell membrane fraction after ASA (40 mM) stimulation. PKC betaI expression markedly decreased in response to ASA treatment. This process was independent of caspase activation because no caspase inhibitors used (i.e., inhibitors to caspase 3, 6, 7, 8, and total caspase activity) significantly changed PKC processing, although inhibition of caspase cascade activity markedly attenuated the apoptosis induced by ASA as measured by DNA-histone complex formation. Upstream PKC signaling induced by ASA seems to play an important role in the regulation of apoptosis because PKC inhibitors significantly reduced the magnitude of DNA-histone complex formation. We conclude that ASA-induced apoptosis in gastric cancer cells is mediated, at least in part, through a PKC mechanism involving the (alpha) and (beta) isoforms and that PKC signaling operates upstream of the caspase cascade, which when activated elicits its downstream effects on DNA degradation.
Redlak
Maria J
MJ
Medical College of Virginia Campus of Virginia Commonwealth University, P.O. Box 980645, Richmond, VA 23298-0568, USA.
Power
Jacinda J
JJ
Miller
Thomas A
TA
D000230:Adenocarcinoma / Q000503:physiopathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D017209:Apoptosis; D001241:Aspirin / Q000009:adverse effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D011493:Protein Kinase C; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000503:physiopathology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011493:Protein Kinase C; D020169:Caspases; D001241:Aspirin