Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2017; 23(27): 4910-4919
Published online Jul 21, 2017. doi: 10.3748/wjg.v23.i27.4910
Generation of glyceraldehyde-derived advanced glycation end-products in pancreatic cancer cells and the potential of tumor promotion
Takanobu Takata, Tadashi Ueda, Akiko Sakasai-Sakai, Masayoshi Takeuchi
Takanobu Takata, Tadashi Ueda, Akiko Sakasai-Sakai, Masayoshi Takeuchi, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan
Author contributions: Takata T and Takeuchi M designed the research; Takata T performed the research; Takeuchi M contributed the reagents that were indispensable for this investigation; Takata T, Ueda T and Sakasai-Sakai A analyzed the data; Takata T and Takeuchi M wrote the paper.
Supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant, No. 25282029, No. 26750056, and No. 16H01811; and a grant from the Hokkoku Foundation for Cancer Research.
Institutional review board statement: This study does not need to be reviewed and approved by the Kanazawa Medical University because the experiment only used an established cell line (PANC-1) and the cell line was not genetically modified.
Conflict-of-interest statement: The authors declare no competing financial interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Takanobu Takata, PhD, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. takajjjj@kanazawa-med.ac.jp
Telephone: +81-76-2862211 Fax: +81-76-2863652
Received: March 24, 2017
Peer-review started: April 10, 2017
First decision: April 26, 2017
Revised: May 10, 2017
Accepted: June 18, 2017
Article in press: June 19, 2017
Published online: July 21, 2017
Processing time: 117 Days and 18.4 Hours
Abstract
AIM

To determine the possibility that diabetes mellitus promotes pancreatic ductal adenocarcinoma via 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 P < 0.01). Cells treated with 2 and 4 mmol/L GA produced 6.4 and 21.2 μg/mg protein of GA-AGEs, respectively (P < 0.05 and P < 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 (P < 0.05 and P < 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.

Keywords: Tumor promotion; Glyceraldehyde-derived advanced glycation-end products; Pancreatic ductal adenocarcinoma

Core tip: The mechanisms promoting pancreatic ductal adenocarcinoma (PDAC) in the pancreas of Type 2 diabetes mellitus patients have not yet been elucidated. We hypothesized that glyceraldehyde (GA)-derived advanced glycation-end products (GA-AGEs) promote PDAC. PANC-1 cells were treated with GA, which induced the production of intracellular GA-AGEs and cell death. The high-molecular-weight complexes of heat shock proteins were produced after GA treatment in a dose-dependent manner. GA-AGEs-bovine serum albumin promoted the proliferation of PANC-1 cells. Although intracellular GA-AGEs induce pancreatic cancer cell death, their secretion and release may promote the proliferation of other pancreatic cancer cells.