title: Antitumor activity of paederosidic acid in human non-small cell lung cancer cells via inducing mitochondria-mediated apoptosis.
abstract: This study was aimed to investigate antitumor activity of paederosidic acid (PA) in human non-small cell lung cancer cells and explore the related mechanisms. The anti-proliferative effects of PA on A549 cells were evaluated by MTT method and the IC50values were calculated. Furthermore, the PA-induced apoptosis in A549 cells was determined by fluorescence microscope via staining with DAPI and by flow cytometer via staining with FITC conjugated Annexin V/PI. The expression of apoptosis-related or signaling proteins was investigated by Western blotting. Our results demonstrated that PA showed significant anti-tumor activity on lung cancer in vitro; the mechanisms were involved in inducing mitochondria-mediated apoptosis via up-regulation of caspase-3, caspase-8, caspase-9, Bid, Bax, down-regulation of Bcl-2 and stimulating the release of Cyto-C from mitochondria. In addition, JNK phosphorylation levels significantly increased concomitantly with decrease in Akt phosphorylation after treatment with PA in A549 cells. However, JNK siRNA-transfected cells diminished PA-induced caspase-3, 8 and 9, Bid and Bax activaton while enhanced the Bcl-2 activation. Collectively, these results indicated that PA-induced JNK activation played an important functional role in apoptosis.
authors.affiliation: Department of Nutrition, Yantaishan Hospital, Yantai 264000, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Center Drug Store, Yantai City Hospital for Infectious Diseases, Yantai 264000, PR China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Infectious Disease, Yantaishan Hospital, Yantai 264000, PR China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Stomatology, Yeda Hospital of Yantai City, Yantai 264006, PR China. Electronic address: doctormengyu@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Meng
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D006574:Heterocyclic Compounds, 2-Ring; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C000588809:paederosidic acid; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: A549; Apoptosis; Lung cancers; Paederosidic acid