title: A novel compound RY10-4 induces apoptosis and inhibits invasion via inhibiting STAT3 through ERK-, p38-dependent pathways in human lung adenocarcinoma A549 cells.
abstract: Previous reports suggested that protoapigenone showed remarkable antitumor activities against a broad spectrum of human cancer cell lines, but had no effect on human lung adenocarcinoma A549 cell. The lack of effective remedies had necessitated the application of new therapeutic scheme. A novel compound RY10-4 which has the similar structure close to protoapigenone showed better antitumor activity. Treatment with RY10-4 inhibited the expression of pro-caspase-3, pro-caspase-9, Bcl-2 as well as phosphorylation of signal transducer and activator of transcription-3 (p-STAT3). It also reduced the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and increases the expressions of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase (TIMP) via inhibiting STAT3 by activating the mitogen-activated protein (MAP) kinases (the c-Jun N-terminal kinase (JNK), the p38 and extracellular signal-regulated kinase (ERK)) in A549 cells treated with RY10-4. Moreover, the cytotoxic effect of RY10-4 was induction of apoptosis in A549 cells by enhancing production of reactive oxygen species (ROS). Taken together, the observations suggested that RY10-4 had affected Bcl-2 family members, caspases, MMPs, TIMPs expressions and ROS production via inhibiting STAT3 activities through ERK and p38 pathways in A549 cells.
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Xue
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: School of Life Science, Wuchang University of Technology, Wuhan 430223, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Yale Medical School, New Haven, CT 06510, USA.
authors.forename: Qianying
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: Chaomei
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China. Electronic address: jinlan8152@163.com.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Ruan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: C574037:2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one; D000970:Antineoplastic Agents; D011753:Pyrones; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor
keywords: ERK; Lung cancer; RY10-4; STAT3; p38