| 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 |
| Guo, Chuan-Long1,2,3 ; Wang, Li-Jun1,2; Zhao, Yue1,2; Liu, Hua1,2,3; Li, Xiang-Qian1,2; Jiang, Bo1,2; Luo, Jiao1,2,3; Guo, Shu-Ju1,2; Wu, Ning1,2; Shi, Da-Yong1,2,3
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| 2018-02-01
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| 发表期刊 | MARINE DRUGS
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| ISSN | 1660-3397
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| 卷号 | 16期号:2页码:13 |
| 通讯作者 | Shi, Da-Yong([email protected])
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| 摘要 | 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, (m)), 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. |
| 关键词 | bromophenol
molecular mechanisms
apoptosis
cell cycle
PI3K
Akt
p38
ERK
ROS
human lung cancer
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| DOI | 10.3390/md16020043
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| 收录类别 | SCI
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| 语种 | 英语
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| 资助项目 | National Natural Science Foundation of China[81773586]###283; National Natural Science Foundation of China[81703354]###282; Key research and development project of Shandong province[2016GSF201193]###551; Key research and development project of Shandong province[2016ZDJS07A13]###285; Key research and development project of Shandong province[2016GSF115002]###552; Key research and development project of Shandong province[2016GSF115009]###553; 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]###1574; NSFC-Shandong Joint Fund for Marine Science Rearch Centers[U1606403]###1209; Scientific and Technological Innovation Project - Qingdao National Laboratory for Marine Science and Technology[2015ASKJ02]###218; AoShan Talents Program - Qingdao National Laboratory for Marine Science and Technology[2015ASTP]###727; National Program for the Support of Top-notch Young Professionals###1575; Taishan scholar Youth Project of Shandong province###558; National Natural Science Foundation of China[81773586]; National Natural Science Foundation of China[81703354]; Key Research and Development Project of Shandong province[2016GSF201193]; Key Research and Development Project of Shandong province[2016ZDJS07A13]; Key Research and Development Project of Shandong province[2016GSF115002]; Key Research and Development Project of Shandong province[2016GSF115009]; 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]; NSFC-Shandong Joint Fund for Marine Science Rearch Centers[U1606403]; Scientific and Technological Innovation Project - Qingdao National Laboratory for Marine Science and Technology[2015ASKJ02]; Aoshan Talents Program - Qingdao National Laboratory for Marine Science and Technology[2015ASTP]; National Program for the Support of Top-notch Young Professionals; Taishan scholar Youth Project of Shandong province |
| WOS研究方向 | Pharmacology & Pharmacy
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| WOS类目 | Chemistry, Medicinal
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| WOS记录号 | WOS:000427528800005
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| 出版者 | MDPI
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| 引用统计 |
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.qdio.ac.cn/handle/337002/158426
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| 专题 | 实验海洋生物学重点实验室
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| 通讯作者 | Shi, Da-Yong |
| 作者单位 | 1.Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao 266071, Peoples R China
3.Univ Chinese Acad Sci, Beijing 10049, Peoples R China
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| 第一作者单位 | 实验海洋生物学重点实验室
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| 通讯作者单位 | 实验海洋生物学重点实验室
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推荐引用方式
GB/T 7714 |
Guo, Chuan-Long,Wang, Li-Jun,Zhao, Yue,et al. 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[J]. MARINE DRUGS,2018,16(2):13.
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| APA |
Guo, Chuan-Long.,Wang, Li-Jun.,Zhao, Yue.,Liu, Hua.,Li, Xiang-Qian.,...&Shi, Da-Yong.(2018).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.MARINE DRUGS,16(2),13.
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| MLA |
Guo, Chuan-Long,et al."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".MARINE DRUGS 16.2(2018):13.
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