title: 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, a polymethoxyflavone, exerts antitumor effect on PI3K/Akt signaling pathway in human gastric cancer cell BGC-7901.
abstract: 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), a polymethoxyflavone (PMF) mainly found in citrus plants, exhibits excellent physiological functions. In this study, we aimed to investigate the anticancer activity of 5HHMF against human gastric cancer cell BGC-7901 both in vitro and in vivo and illustrate the potential mechanisms. The proliferation of BGC-7901 cells was assessed by MTT assay. Reactive oxygen species (ROS) level was determined by ELISA kit. The protein expression was determined by western blot analysis. Antitumor activity of 5HHMF in vivo was evaluated in BALB/c nude mice. The results showed that treatment with 5HHMF significantly suppressed BGC-7901 cells proliferation, increased ROS generation, and upregulated cytochrome c release from the mitochondria to the cytosol. Western blot analysis demonstrated that 5HHMF significantly downregulated the expression of procaspase-3, procaspase-9, and PARP and upregulated cleaved caspase-3, cleaved caspase-9, cleaved PARP, and Bax/Bcl-2 ratio. Meanwhile, 5HHMF treatment markedly decreased the expression of PI3K and p-Akt. In addition, 5HHMF effectively inhibited tumor growth in xenograft models in BALB/c nude mice without major side action. In summary, 5HHMF-induced apoptosis via targeting PI3K/Akt, indicating 5HHMF is a potential antitumor agent for gastric cancer.
authors.affiliation: a Department of General Surgery , Wendeng Central Hospital of Weihai , Weihai , China and.
authors.forename: Xinjian
authors.initials: X
authors.lastname: Wang
authors.affiliation: b Endoscopy Room, Wendeng Central Hospital of Weihai , Weihai , China.
authors.forename: Min
authors.initials: M
authors.lastname: Xia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047309:Flavones / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D051058:Oncogene Protein v-akt / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D047309:Flavones; D017382:Reactive Oxygen Species; C521815:5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: 5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone; PI3K/Akt; ROS; antitumor; gastric cancer