A novel compound RY10-4 induces apoptosis and inhibits invasion via Cross inhibiting STAT3 through ERK-, p38-dependent pathways in human lung adenocarcinoma A549 cells

作者：Xue, Pingping; Zhao, Yang; Liu, Yang; Yuan, Qianying; Xiong, Chaomei; Ruan, Jinlan^*

来源：Chemico-Biological Interactions, 2014, 209: 25-34.

DOI：10.1016/j.cbi.2013.11.014

• RY10-4
• ERK
• p38
• STAT3
• Lung cancer

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 (INK), 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.

• 出版日期2014-2-25
• 单位华中科技大学