title: The H+/K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells.
abstract: Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 μg/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment.
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Qiaoyin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Nianyu
authors.initials: N
authors.lastname: Huang
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Huajun
authors.initials: H
authors.lastname: Luo
authors.forename: Haibo
authors.initials: H
authors.lastname: He
authors.forename: Mingruo
authors.initials: M
authors.lastname: Ding
authors.forename: Wei-Qiao
authors.initials: WQ
authors.lastname: Deng
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009853:Omeprazole / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000201:enzymology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D013270:Stomach / Q000187:drug effects* / Q000201:enzymology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000201:enzymology; D055454:Trametes / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000897:Anti-Ulcer Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D054328:Proton Pump Inhibitors; D014315:Triterpenes; C586576:trametenolic acid B; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole
keywords: Anti-gastric cancer; Docking simulation; H(+)/K(+)-ATPase inhibitory activity; Trametenolic acid B