8 304

Cited 85 times in

Selective induction of apoptosis with proton pump inhibitor in gastric cancer cells.

Authors
Yeo, M; Kim, DK; Kim, YB; Oh, TY; Lee, JE; Cho, SW; Kim, HC; Hahm, KB
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 10(24):8687-8696, 2004
Journal Title
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN
1078-0432
Abstract
PURPOSE: To survive in an ischemic microenvironment with a lower extracellular pH, ability to up-regulate proton extrusion is critical for cancer cell survival. Gastric H+/K(+)-ATPase exchanges luminal K+ for cytoplasmic H+ and is the enzyme primarily responsible for gastric acidification. On the basis of the fact that blocking the clearance of acidic metabolites are known to induce the cell death, we hypothesized that pantoprazole (PPZ), one of gastric H+/K(+)-ATPase inhibitors used frequently to treat acid-related diseases, could inhibit growth of tumor cells.



EXPERIMENTAL DESIGN: Genomic DNA fragmentation, terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling assay, and annexin V staining were performed to detect PPZ-induced apoptosis. Mitogen-activated protein kinase activation and heat shock proteins expression were determined by immunoblot with specific antibodies. The antitumor effect of PPZ was evaluated in vivo by a xenograft model of nude mice.



RESULTS: After PPZ treatment, apoptotic cell death was seen selectively in cancer cells and was accompanied with extracellular signal-regulated kinase deactivation. By contrast, normal gastric mucosal cells showed the resistance to PPZ-induced apoptosis through the overexpression of antiapoptotic regulators including HSP70 and HSP27. In a xenograft model of nude mice, administration of PPZ significantly inhibited tumorigenesis and induced large-scale apoptosis of tumor cells.



CONCLUSIONS: PPZ selectively induced in vivo and in vitro apoptotic cell death in gastric cancer, suggesting that proton pump inhibitors could be used for selective anticancer effects.
MeSH terms
2-PyridinylmethylsulfinylbenzimidazolesAnimalsAnnexin A5/metabolismAnti-Ulcer Agents/*pharmacologyApoptosis/*drug effectsBenzimidazoles/*pharmacologyBiological Transport/physiologyEnzyme Activation/drug effectsFibroblasts/enzymologyH(+)-K(+)-Exchanging ATPase/*antagonists & inhibitors/metabolismHeat-Shock Proteins/metabolismHumansIn Situ Nick-End LabelingIntestinal Mucosa/enzymologyMiceMice, NudeMitogen-Activated Protein Kinases/metabolismOmeprazole/*analogs & derivatives/pharmacologyProton PumpsRatsStomach Neoplasms/*drug therapy/*enzymology/pathologySulfoxides/*pharmacologyTransplantation, HeterologousTumor Cells, Cultured
DOI
10.1158/1078-0432.CCR-04-1065
PMID
15623654
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
AJOU Authors
김, 영배조, 성원함, 기백
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse