title: Licochalcone A-induced human gastric cancer BGC-823 cells apoptosis by regulating ROS-mediated MAPKs and PI3K/AKT signaling pathways.
abstract: Both phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen activated protein kinase (MAPK) signaling cascades play an important role in cell proliferation, survival, angiogenesis, and metastasis of tumor cells. In the present report, we investigated the effects of licochalcone A (LA), a flavonoid extracted from licorice root, on the PI3K/AKT/mTOR and MAPK activation pathways in human gastric cancer BGC-823 cells. LA increased reactive oxygen species (ROS) levels, which is associated with the induction of apoptosis as characterized by positive Annexin V binding and activation of caspase-3, and cleavage of poly-ADP-ribose polymerase (PARP). Inhibition of ROS generation by N-acetylcysteine (NAC) significantly prevented LA-induced apoptosis. Interestingly, we also observed that LA caused the activation of ERK, JNK, and p38 MAPK in BGC-823 cells. The antitumour activity of LA-treated BGC-823 cells was significantly distinct in KM mice in vivo. All the findings from our study suggest that LA can interfere with MAPK signaling cascades, initiate ROS generation, induce oxidative stress and consequently cause BGC cell apoptosis.
authors.affiliation: Binzhou medical University, Yantai, 264003, Shandong, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Hao
authors.affiliation: The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Binzhou medical University, Yantai, 264003, Shandong, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.affiliation: Binzhou medical University, Yantai, 264003, Shandong, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Gao
authors.affiliation: Binzhou medical University, Yantai, 264003, Shandong, China.
authors.forename: Xiling
authors.initials: X
authors.lastname: Sun
authors.affiliation: Qianfoshan Hospital of Shandong University, Jinan, 250014, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: 1] Binzhou medical University, Yantai, 264003, Shandong, China [2] Key Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002, Xinjiang, China.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D047188:Chalcones; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C070840:licochalcone A