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Mar. Drugs 2018, 16(2), 43; https://doi.org/10.3390/md16020043

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

1,2,3,†
,
1,2,†
,
1,2
,
1,2,3
,
1,2
,
1,2
,
1,2,3
,
1,2
,
1,2
and
1,2,3,*
1
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
2
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China
3
University of Chinese Academy of Sciences, Beijing 10049, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 5 December 2017 / Revised: 18 January 2018 / Accepted: 23 January 2018 / Published: 25 January 2018
(This article belongs to the Collection Marine Compounds and Cancer)
Full-Text   |   PDF [5209 KB, uploaded 25 January 2018]   |  

Abstract

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. View Full-Text
Keywords: bromophenol; molecular mechanisms; apoptosis; cell cycle; PI3K/Akt; p38/ERK; ROS; human lung cancer bromophenol; molecular mechanisms; apoptosis; cell cycle; PI3K/Akt; p38/ERK; ROS; human lung cancer
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Guo, C.-L.; Wang, L.-J.; Zhao, Y.; Liu, H.; Li, X.-Q.; Jiang, B.; Luo, J.; Guo, S.-J.; Wu, N.; Shi, D.-Y. 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. Mar. Drugs 2018, 16, 43.

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