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.

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

“…Apoptosis is a controlled form of cell death that can lead to various morphological changes, such as nuclear pyknosis, cell surface changes, and chromosome condensation . We examined morphological changes by Hoechst 33258 staining and show that A549 cells treated with SCU display specific apoptotic changes in a concentration‐dependent manner.…”

“…Apoptosis is a controlled form of cell death that can lead to various morphological changes, such as nuclear pyknosis, cell surface changes, and chromosome condensation. 25,26 We examined morphological changes by Hoechst 33258 staining and show that A549 cells treated with SCU display specific apoptotic changes in a concentration-dependent manner. Flow cytometry was used to externalize phosphatidylserine (cell surface changes) in A549 cells and our results show that the percentage of apoptotic cells is markedly increased in a concentration-dependent manner.…”

Cordycepin induces apoptosis in human bladder cancer T24 cells through ROS-dependent inhibition of the PI3K/Akt signaling pathway

“…Among them, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in the inhibition of apoptosis and the promotion of cell growth, thus playing a key role in the pathogenesis of various tumors (6)(7)(8). Moreover, there is growing interest in reactive oxygen species (ROS), which induce apoptosis of cancer cells through dysregulation of the PI3K/Akt signaling pathway (9)(10)(11). Therefore, inhibiting the PI3K/Akt signaling pathway, while promoting the generation of ROS, can be an attractive approach to cancer treatment.…”

The Fluoro-Thiazolylhydrazone Compound TSC-3C Inhibits Triple Negative Breast Cancer (TNBC) Cell Line Activity by Promoting Apoptosis, Regulating the MAPK Pathway and Inducing Mitochondrial Dysfunction

“…Although few potent compounds have been previously reported [28][29][30]35,43], the anti-TNBC activity of fluoro-thiazolylhydrazone hybrids is reported for the first time in this work. The anticancer activity of TSC-3C for TNBC is evidence for a promising therapeutic agent that is important for drug discovery and clinical applications.…”