A Novel Bromophenol Derivative BOS-102 Induces Cell Cycle Arrest and Apoptosis in Human A549 Lung Cancer Cells via ROS-Mediated PI3K/Akt and the MAPK Signaling Pathway
Chuan-Long Guo,
Li-Jun Wang,
Yue Zhao,
Hua Liu,
Xiang-Qian Li,
Bo Jiang,
Jiao Luo,
Shu-Ju Guo,
Ning Wu,
Da-Yong Shi
Affiliations
Chuan-Long Guo
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Li-Jun Wang
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Yue Zhao
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Hua Liu
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Xiang-Qian Li
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Bo Jiang
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Jiao Luo
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Shu-Ju Guo
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Ning Wu
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Da-Yong Shi
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
Bromophenol is a type of natural marine product. It has excellent biological activities, especially anticancer activities. In our study of searching for potent anticancer drugs, a novel bromophenol derivative containing indolin-2-one moiety, 3-(4-(3-([1,4′-bipiperidin]-1′-yl)propoxy)-3-bromo-5-methoxybenzylidene)-N-(4-bromophenyl)-2-oxoindoline-5-sulfonamide (BOS-102) was synthesized, which showed excellent anticancer activities on human lung cancer cell lines. A study of the mechanisms indicated that BOS-102 could significantly block cell proliferation in human A549 lung cancer cells and effectively induce G0/G1 cell cycle arrest via targeting cyclin D1 and cyclin-dependent kinase 4 (CDK4). BOS-102 could also induce apoptosis, including activating caspase-3 and poly (ADP-ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive oxygen species (ROS) generation, decreasing mitochondrial membrane potential (MMP, ΔΨm), and leading cytochrome c release from mitochondria. Further research revealed that BOS-102 deactivated the PI3K/Akt pathway and activated the mitogen-activated protein kinase (MAPK) signaling pathway resulting in apoptosis and cell cycle arrest, which indicated that BOS-102 has the potential to develop into an anticancer drug.
