No abstract

Our previous study discovered that isoliensinine (isolie) triggers hepatocellular carcinoma (HCC) cell apoptosis via inducing p65 dephosphorylation at Ser536 and inhibition of NF-κB. Here, we showed that isolie promoted p65/PP2A interaction in vitro and in vivo. Repression of PP2A activity or knockdown of the expression of PP2A-C (the catalytic subunit of PP2A) abrogated isolie-provoked p65 dephosphorylation. I2PP2A is an endogenous PP2A inhibitor. Isolie directly impaired PP2A/I2PP2A interaction. Knockdown of I2PP2A boosted p65/PP2A association and p65 dephosphorylation. Overexpression of I2PP2A restrained isolie-induced p65 dephosphorylation. Untransformed hepatocytes were insensitive to isolie-induced NF-κB inhibition and cell apoptosis. In these cells, basal levels of I2PP2A and p65 phosphorylation at Ser536 were lower than in HCC cells. These findings collectively indicated that isolie suppresses NF-κB in HCC cells through impairing PP2A/I2PP2A interaction and stimulating PP2A-dependent p65 dephosphorylation at Ser536.

In this study, PEGylated nanoparticles quercetin drug delivery vehicles were investigated as carriers for anticancer drugs induced programed cell death (PCD). PEG2000-DPSE-coated quercetin nanoparticles were prepared and tumor cell killing efficacy was studied on glioma C6 cells and assayed for cell survival, apoptosis, or necrosis. The levels of ROS production and mitochondrial membrane potential (ΔΨm) were determined. Western blot assayed p53, p-p53, cytochrome C, and caspase proteins expression were also studied. Results indicate that PEG2000-DPSE-QUE-NPS showed dose-dependent cytotoxicity to C6 glioma cells and enhanced ROS accumulation induced upregulation of p53 protein, which was accompanied with an increase in cytochrome c and caspase-3 protein levels. These results support the hypothesis that quercetin nanoparticles-coated PEG2000-DPSE remarkably enhanced anticancer effect of induced programed cell death on C6 glioma cells. Overall, PEG2000-DPSE-coated quercetin nanoparticles showed promising potential as a drug carrier for cancer therapy.