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BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway
Guo, Chuanlong1,2; Wang, Lijun1,2; Zhao, Yue1,2; Jiang, Bo1,2; Luo, Jiao1,2; Shi, Dayong1,2
2019-05-01
Source PublicationEXPERIMENTAL AND THERAPEUTIC MEDICINE
ISSN1792-0981
Volume17Issue:5Pages:3848-3858
Corresponding AuthorShi, Dayong(shidayong@qdio.ac.cn)
AbstractThe novel bromophenol derivative, 3-(3-bromo-5-methoxy-4-(3-(piperidin-1-yl)propoxy)benzylidene)-N-(4-bromophenyl)-2-oxoindoline-5-sulfonamide (BOS-93), was synthesized in the CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences (Qingdao, China). Experimental studies have demonstrated that it could induce apoptosis and autophagy in human A549 lung cancer cells, and it could also inhibit tumor growth in human A549 lung cancer xenograft models. In the present study, the molecular pathways underlying these effects were identified. The results demonstrated that BOS-93 could inhibit cell proliferation in A549 cells and block A549 cells at the G0/G1 phase. Furthermore, BOS-93 could induce apoptosis, activate caspase-3 and poly ADP ribose polymerase, and increase the B cell lymphoma (Bcl)-2 associated X protein/Bcl-2 ratio. Notably, BOS-93 could also induce autophagy in A549 cells. BOS-93-induced autophagy was confirmed by detecting light chain 3 (LC3)-I/LC3-II conversion and increasing expression of beclin1 and autophagy-related gene 14. Notably, BOS-93-induced autophagy could be inhibited by the autophagy inhibitor 3-MA. Flow cytometry, transmission electron microscopy (TEM) and western blot analysis indicated that BOS-93 induced apoptosis and autophagy activities by deactivating phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and activating the mitogen-activated protein kinase signaling pathway. The present findings indicated that BOS-93 might be a novel anti-cancer agent for treatment of human lung cancer.
Keywordbromophenol apoptosis autophagy phosphoinositide 3-kinase protein kinase B mechanistic target of rapamycin signaling reactive oxygen species
DOI10.3892/etm.2019.7402
Indexed BySCI
Language英语
Funding ProjectNational Natural Science Foundation of China[81773586] ; National Natural Science Foundation of China[81703354] ; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014] ; Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences[ZSTH-026] ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; National Program for Support of Top-notch Young Professionals ; Taishan Scholar Youth Project of Shandong Province
WOS Research AreaResearch & Experimental Medicine
WOS SubjectMedicine, Research & Experimental
WOS IDWOS:000466935600072
PublisherSPANDIDOS PUBL LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/161259
Collection实验海洋生物学重点实验室
Corresponding AuthorShi, Dayong
Affiliation1.Chinese Acad Sci, Inst Oceanol, CAS Key Lab Expt Marine Biol, 7 Nanhai Rd, Qingdao 266071, Shandong, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266071, Shandong, Peoples R China
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Guo, Chuanlong,Wang, Lijun,Zhao, Yue,et al. BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway[J]. EXPERIMENTAL AND THERAPEUTIC MEDICINE,2019,17(5):3848-3858.
APA Guo, Chuanlong,Wang, Lijun,Zhao, Yue,Jiang, Bo,Luo, Jiao,&Shi, Dayong.(2019).BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway.EXPERIMENTAL AND THERAPEUTIC MEDICINE,17(5),3848-3858.
MLA Guo, Chuanlong,et al."BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway".EXPERIMENTAL AND THERAPEUTIC MEDICINE 17.5(2019):3848-3858.
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