BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway

doi:10.3892/etm.2019.7402

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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, Chuanlong 1,2; Wang, Lijun 1,2; Zhao, Yue 1,2; Jiang, Bo 1,2; Luo, Jiao 1,2; Shi, Dayong 1,2
	2019-05-01
发表期刊	EXPERIMENTAL AND THERAPEUTIC MEDICINE
ISSN	1792-0981
卷号	17 期号:5 页码:3848-3858
通讯作者	Shi, Dayong([email protected])
摘要	The 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.
关键词	bromophenol apoptosis autophagy phosphoinositide 3-kinase protein kinase B mechanistic target of rapamycin signaling reactive oxygen species
DOI	10.3892/etm.2019.7402
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81773586]###283; National Natural Science Foundation of China[81703354]###282; Key Research Program of Frontier Sciences, CAS[QYZDB-SSW-DQC014]###580; Project of Discovery, Evaluation and Transformation of Active Natural Compounds, Strategic Biological Resources Service Network Programme of Chinese Academy of Sciences[ZSTH-026]###932; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722]###556; National Program for Support of Top-notch Young Professionals###557; Taishan scholar Youth Project of Shandong province###558; National 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研究方向	Research & Experimental Medicine
WOS类目	Medicine, Research & Experimental
WOS记录号	WOS:000466935600072
出版者	SPANDIDOS PUBL LTD
引用统计	被引频次：15[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/161259
专题	实验海洋生物学重点实验室
通讯作者	Shi, Dayong
作者单位	1.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
第一作者单位	中国科学院海洋研究所
通讯作者单位	中国科学院海洋研究所
推荐引用方式 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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