Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion.

AIM

To determine the possibility that diabetes mellitus promotes pancreatic ductal adenocarcinoma glyceraldehyde (GA)-derived advanced glycation-end products (GA-AGEs).

METHODS

PANC-1, a human pancreatic cancer cell line, was treated with 1-4 mmol/L GA for 24 h. The cell viability and intracellular GA-AGEs were measured by WST-8 assay and slot blotting. Moreover, immunostaining of PANC-1 cells with an anti-GA-AGE antibody was performed. Western blotting (WB) was used to analyze the molecular weight of GA-AGEs. Heat shock proteins 90α, 90β, 70, 27 and cleaved caspase-3 were analyzed by WB. In addition, PANC-1 cells were treated with GA-AGEs-bovine serum albumin (GA-AGEs-BSA), as a model of extracellular GA-AGEs, and proliferation of PANC-1 cells was measured.

RESULTS

In PANC-1 cells, GA induced the production of GA-AGEs and cell death in a dose-dependent manner. PANC-1 cell viability was approximately 40% with a 2 mmol/L GA treatment and decreased to almost 0% with a 4 mmol/L GA treatment (each significant difference was < 0.01). Cells treated with 2 and 4 mmol/L GA produced 6.4 and 21.2 μg/mg protein of GA-AGEs, respectively ( < 0.05 and < 0.01). The dose-dependent production of some high-molecular-weight (HMW) complexes of HSP90β, HSP70, and HSP27 was observed following administration of GA. We considered HMW complexes to be dimers and trimers with GA-AGEs-mediated aggregation. Cleaved caspase-3 could not be detected with WB. Furthermore, 10 and 20 μg/mL GA-AGEs-BSA was 27% and 34% greater than that of control cells, respectively ( < 0.05 and < 0.01).

CONCLUSION

Although intracellular GA-AGEs induce pancreatic cancer cell death, their secretion and release may promote the proliferation of other pancreatic cancer cells.