title: Role of proton pump inhibitors in preventing hypergastrinemia-associated carcinogenesis and in antagonizing the trophic effect of gastrin.
abstract: Gastrin is the main hormone stimulating gastric acid secretion, but it exerts proliferative and anti-apoptotic actions on various cancer cell types, in addition to its well-known trophic effect on enterochromaffin-like cells. As treatment with proton pump inhibitors (PPIs) increases the biosynthesis and secretion of gastrin, it has been postulated that treatment with PPIs could increase the risk of cancer, especially in Barrett's esophagus, gastric carcinoids, and colorectal cancer (CRC). Some tumors produce gastrin of their own, which can act in an autocrine manner to promote tumor growth. In addition, gastrin is known to foster the tumor microenvironment. However, in spite of these potentially increased cancer risks due to PPI-induced hypergastrinemia, prospective, large-scale cohort studies did not show an increase in CRC prevalence. The question as to why the long-term use of PPIs was not associated with an increased cancer risk of CRC might be answered by the fact that the PPIs antagonized the trophic effects of hypergastrinemia. Furthermore, the blockade of proton pumps or potassium channels in cancer cells could limit the abnormal glycolytic energy metabolism of cancer cells. Apart from their suppressive effect on gastric acids, PPIs exert an anti-tumor effect through the selective induction of apoptosis as well as an anti-inflammatory effect, and they protect cells from developing chemo- or radiotherapeutic resistance. Moreover, the anti-carcinogenic actions of PPIs were augmented with PPI-induced hypergastrinemia. Together with their potential targeted killing of cancer stem cells, these effects demonstrate their potential anti-cancer actions.
authors.affiliation: CHA Cancer Prevention Research Center, CHA Bio Complex, Seongnam, Korea. hahmkb@cha.ac.kr.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Han
authors.forename: J-M
authors.initials: JM
authors.lastname: Park
authors.forename: N
authors.initials: N
authors.lastname: Kangwan
authors.forename: M
authors.initials: M
authors.lastname: Jeong
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Cho
authors.forename: W J
authors.initials: WJ
authors.lastname: Ko
authors.forename: K B
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D054328:Proton Pump Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D017494:Proton Pumps / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005755:Gastrins; D054328:Proton Pump Inhibitors; D017494:Proton Pumps