title: Effects of diphyllin as a novel V-ATPase inhibitor on gastric adenocarcinoma.
abstract: The natural compound diphyllin, a cytostatic lignan isolated from Cleistanthus collinus, can dramatically inhibit the proliferation and induce the apoptosis of human gastric cancer cells, SGC7901. Our study found that diphyllin can inhibit the expression of V-ATPases in a dose-dependent manner, decrease the internal pH (pHi) and reverse the transmembrane pH gradient in SGC7901 cells. Changes of the pH gradient were positively correlated with diphyllin concentration. Further study found that diphyllin treatment caused a decrease in phospho-LRP6, but not in LRP6. β-catenin in Wnt/β-catenin signaling and its target genes, c-myc and cyclin-D1, were also decreased with the inhibition of V-ATPases. Therefore, diphyllin could be characterized as a new V-ATPase inhibitor in treating gastric cancer and inhibiting the phosphorylation of LRP6 in Wnt/β-catenin signaling.
authors.affiliation: Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.forename: Pengfei
authors.initials: P
authors.lastname: Liu
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Shen
authors.forename: Shuling
authors.initials: S
authors.lastname: Huang
authors.forename: Huimin
authors.initials: H
authors.lastname: Guo
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052117:Benzodioxoles; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005110:Extracellular Space / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000737:chemistry / Q000187:drug effects; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D052117:Benzodioxoles; D004148:Dioxolanes; D004791:Enzyme Inhibitors; D017705:Lignans; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555476:Lrp6 protein, mouse; D025262:Vacuolar Proton-Translocating ATPases; C010130:diphyllin