Poly(allylguanidine)-Coated Surfaces Regulate TGF-β in Glioblastoma Cells to Induce Apoptosis via NF-κB Pathway Activation

Abstract

Polycationic biomaterials are currently widely applied in neuronal cell cultures to promote cell adhesion and viability. However, polycations generally have cytotoxic properties that limit their application in the field of biomaterials. In this study, we examined the use of a novel polycation poly(allylguanidine) (PAG), which contains a guanidine group in the side chain and a structure similar to poly(allylamine hydrochloride) (PAH), an example of another commonly used polycation. Our findings showed that exposure to PAG induced apoptosis in glioblastoma (GBM) cells, while exposure to PAH induced necrosis. Compared to control groups, the PAG coating significantly limited the proliferation of GBM8901 in vitro and in vivo. Furthermore, GBM8901 cells exposed to the PAG coating exhibited increased levels of phospho-p65 and phosphor-IκB, implying that GBM8901 cells underwent apoptotic cell death via the NF-κB pathway by the regulation of TGF-β. This result was further confirmed to be consistent with the experimental results from western blot protein analysis and apoptosis/necrosis assays. These findings indicate that the polycation PAG has the potential to not only suppress the proliferation of GBM8901 cancer cells but also improve the neural viability and promote the differentiation of neural stem/precursor cells into mature neurons. In conclusion, biomaterials such as PAG act as extremely potent options for applications in the treatment of pathological conditions such as brain cancer.

The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma

“…Monacolin K (MK), a polyketo secondary metabolic compound of the mold genus monascus, can downregulate JNK/ERK/P65/IκBα expression and promote the phosphorylation of ERK and p65, ultimately resulting in the apoptosis of GBM cells [ 146 ]. Poly(allylamine hydrochloride) (PAH) can induce GBM cell apoptosis via suppressing TGF-β/p65 signaling [ 147 ]. Meisoindigo, a second-generation derivative of indirubin, can diminish the expression of PI3K, AKT, p-AKT, p65, and p-p65 to result in apoptosis of GBM cells [ 148 ].…”

Targeting the deubiquitinase USP2 for malignant tumor therapy (Review)

“…Glioblastoma (GBM) is an astrocytic tumor characterized by rapid growth, high malignancy and high mortality rates ( 132 ). As a cancer-promoting factor, TGF-β serves an important role in the development of GBM ( 133 , 134 ). SMAD7, a key negative regulator of TGF-β signaling, exerts its inhibitory effects on TGF-β by blocking receptor activity and inducing receptor degradation ( 135 ).…”

Mechanically induced pyroptosis enhanced cardiosphere oxidative stress resistance and metabolism for myocardial infarction therapy

“…Cellular physiological activities could be manipulated by the properties of the contacted substrate 26,27,28 . Liquid crystal patterns could directly introduce cells into a 3D environment and form cell structures in situ 29 , which may be bene cial for mass spheroid production during large-scale clinical applications.…”