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.

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.

• Authors: 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
• Journal: Marine drugs (Mar Drugs) Vol. 16 Issue 2 (Jan 25 2018) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 29370087 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• BOS-102
• Benzyl Compounds
• Indoles
• Phenols
• Piperidines
• Reactive Nitrogen Species
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt

Topics

• A549 Cells
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (biosynthesis, drug effects)
• Benzyl Compounds (chemistry, pharmacology)
• Cell Cycle Checkpoints (drug effects)
• Cell Proliferation (drug effects)
• Humans
• Indoles (chemistry, pharmacology)
• MAP Kinase Signaling System (drug effects)
• Membrane Potential, Mitochondrial (drug effects)
• Oncogene Protein v-akt (metabolism)
• Phenols (chemistry, pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Piperidines (chemistry, pharmacology)
• Reactive Nitrogen Species (metabolism)
• Tumor Stem Cell Assay