title: Matrine induction of reactive oxygen species activates p38 leading to caspase-dependent cell apoptosis in non-small cell lung cancer cells.
abstract: Non-small cell lung carcinoma (NSCLC) is one of the most refractory cancers in the clinic; it is insensitive to chemotherapy and is usually excised. However, screening natural compounds from herbs is also considered a possible method for its therapy. In the present study, we investigated whether matrine, a natural compound isolated from Sophora flavescens Ait. and exerting an inhibitory effect on lung cancer cells, also indicates inhibition on NSCLC cells and elucidated its molecular mechanism. Firstly, it is confirmed that matrine induces apoptosis of human NSCLC cells with anti-apoptotic factors inhibited and dependent on caspase activity. In addition, we found that matrine increases the phosphorylation of p38 but not its total protein, and inhibition of the p38 pathway with SB202190 partially prevents matrine-induced apoptosis. Furthermore, matrine generates reactive oxygen species (ROS) in a dose- and time-dependent manner, which is reversed by pretreatment with N-acetyl-L-cysteine (NAC). Additionally, inhibition of cell proliferation and increase of phosphorylation of p38 was also partially reversed by NAC. Collectively, matrine activates p38 pathway leading to a caspase-dependent apoptosis by inducing generation of ROS in NSCLC cells and may be a potential chemical for NSCLC.
authors.affiliation: College of Pharmacy, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Tan
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Qian
authors.forename: Rongdi
authors.initials: R
authors.lastname: Jia
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Zhongqin
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000235:genetics*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011807:Quinolizines / Q000008:administration & dosage* / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D029909:Sophora / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D000093842:Matrines
chemical_list: D000470:Alkaloids; D007093:Imidazoles; D011725:Pyridines; D011807:Quinolizines; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; D000093842:Matrines